Benzenesulfonamide derivatives and use thereof

ABSTRACT

A benzenesulfonamide derivative represented by the following general formula: ##STR1## wherein R 1  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom; R 2  represents a C 1  -C 10  straight- or branched-chain alkyl group, a C 3  -C 8  cycloalkyl group which may be substituted with one or more C 1  -C 6  alkyl groups on its ring, a C 1  -C 6  alkyl group substituted with one or more C 3  -C 8  cycloalkyl groups, 1-adamantylmethyl group, 2-norbornylmethyl group, or a C 1  -C 6  alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents; R 3  represents a hydrogen atom or a lower alkyl group; and n is an integer of from 2 to 4, and a pharmacologically acceptable salt thereof. The present compounds have thromboxane A 2  antagonistic activity, leucotriene antagonistic activity and the like and useful as a platelet aggregation inhibitor, antithrombotic agent, antiasthmatic agent and antiallergic agent.

This application is a 371 of PCT/JP93/01382 filed Sep. 29, 1993 and published as WO94/07848 Apr. 14, 1994.

TECHNICAL FIELD

The present invention relates to benzenesulfonamide derivatives and their pharmacologically acceptable salts having thromboxane A₂ antagonistic activity, leucotriene antagonistic activity and the like which are useful as platelet aggregation inhibitors, antithrombotic agents, antiasthmatic agents and antiallergic agents, and to uses thereof.

BACKGROUND ART

For example, the U.S. Pat. No. 4,258,058 discloses Sulotroban represented by the following formula and its derivatives: ##STR2## and the U.S. Pat. No. 4,443,477 discloses Daltroban represented by the following formula and its derivatives: ##STR3## as benzenesulfonamide derivatives having thromboxane A₂ antagonistic activity. However, compounds structurally similar to the compounds of the present invention have never been known so far.

Thromboxane A₂ is a potent physiologically active substance which is biosynthesized from arachidonic acid in living bodies. The substance has platelet aggregation activity and contracting activity on smooth muscles such as bronchi and coronary arteries. Although the substance is rather important in living bodies, it is considered that its excessive production may cause various disorders such as thrombosis and asthma. Leucotriene is also a potent physiologically active substance biosynthesized from arachidonic acid. This substance induces various pharmacological effects such as contraction of respiratory tract smooth muscle, hyper-secretion of respiratory tract and hyper-permeation of blood vessels, and is considered to be significantly involved in pathopoiesis of asthma and allergic inflammation.

For these reasons, drugs having thromboxane A₂ antagonistic activity are expected to be useful as preventive and therapeutic agents for diseases associated with thromboxane A₂ such as, for example, ischemic heart diseases such as angina pectoris and myocardial infarction, cerebrovascular diseases, thrombosis, and asthma. Drugs having leucotriene antagonistic activity are also expected to be useful as preventive and therapeutic agents for diseases associated with leucotriene such as, for example, asthma and allergic inflammation. Although several thromboxane A₂ antagonists and leucotriene antagonists have been under clinical trials, they are not commercially available at present. Accordingly, further researches have been desired.

An object of the present invention is thus to provide medicaments having thromboxane A₂ antagonistic activity and leucotriene antagonistic activity and useful as drugs for preventive and therapeutic treatments for ischemic heart diseases such as angina pectoris and myocardial infarction, cerebrovascular diseases, thrombosis, and asthma, or useful as drugs for preventive and therapeutic treatments for asthma and allergic inflammation.

The inventors of the present invention conducted various studies under these circumstances and, as a result, found that the novel benzenesulfonamide derivatives of the present invention have inhibitory activities against thromboxane A₂ synthetase in addition to thromboxane A₂ antagonistic activities and leucotriene D₄ antagonistic activities. The inventors also found that they are highly useful as platelet aggregation inhibitors, antithrombotic agents, antiasthmatic agents and antiallergic agents. The present invention was achieved on the basis of these findings.

DISCLOSURE OF THE INVENTION

According to the present invention, there are provided novel benzenesulfonamide derivatives represented by the following general Formula (I): ##STR4## wherein R¹ represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom; R² represents a C₁ -C₁₀ straight- or branched-chain alkyl group, a C₃ -C₈ cycloalkyl group which may be substituted with one or more C₁ -C₆ alkyl groups on its ring, a C₁ -C₆ alkyl group substituted with one or more C₃ -C₈ cycloalkyl groups, 1-adamantylmethyl group, 2-norbornylmethyl group, or a C₁ -C₆ alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents; R³ represents a hydrogen atom or a lower alkyl group; and n is an integer of from 2 to 4, and pharmacologically acceptable salts thereof.

According to the present invention, there are also provided platelet aggregation inhibitors or antithrombotic agents, antiasthmatic agents, and antiallergic agents comprising one or more of the aforementioned benzenesulfonamide derivatives or pharmacologically acceptable salts thereof as active ingredients.

BEST MODE FOR CARRYING OUT THE INVENTION

According to a preferred embodiment of the present invention, there are provided compounds of the above-described general Formula (I) and their pharmacologically acceptable salts and the uses thereof, wherein R¹ represents a halogen atom; R² represents a C₄ -C₈ straight- or branched-chain alkyl group or a C₁ -C₂ alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents; R³ represents a hydrogen atom or a lower alkyl group; and n is 3.

In addition, according to a particularly preferred embodiment of the present invention, there are provided compounds of the above-described general Formula (I) and their pharmacologically acceptable salts and the uses thereof, wherein R¹ represents a halogen atom; R² represents a C₄ -C₈ straight- or branched-chain alkyl group, or benzyl group or phenethyl group which may be substituted with one or more halogen atoms or lower alkyl groups; R³ represents a hydrogen atom or a lower alkyl group; and n is 3.

In the aforementioned general Formula (I), examples of the lower alkyl group represented by R¹ and R³ include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. Examples of the lower alkoxy group represented by R¹ include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, and tert-butoxy group. As the halogen atom, fluorine atom, chlorine atom, bromine atom or iodine atom may be used.

Examples of the straight- or branched-chain C₁ -C₁₀ alkyl group represented by R² include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, n-hexyl group, isohexyl group, 3,3-dimetylbutyl group, n-heptyl group, 5-methylhexyl group, 4,4-dimethylpentyl group, n-octyl group, 5,5-dimethylhexyl group, n-nonyl group, and n-decyl group. Examples of the C₃ -C₈ cycloalkyl group which may be substituted with one or more C₁ -C₆ alkyl groups on its ring include, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, cyclohexyl group, 4-methylcyclohexyl group, 4-ethylcyclohexyl group, 4-propylcyclohexyl group, 4-butylcyclohexyl group, 4-pentylcyclohexyl group, 4-hexylcyclohexyl group, 2-methylcyclohexyl group, 3-methylcyclohexyl group, cycloheptyl group, and cyclooctyl group. Examples of the C₁ -C₆ alkyl group substituted with one ore more C₃ -C₈ cycloalkyl groups include, for example, cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, 2-cyclopentylethyl group, cyclohexylmethyl group, 2-cyclohexylethyl group, 3-cyclohexylpropyl group, 4-cyclohexylbutyl group, 5-cyclohexylpentyl group, 6-cyclohexylhexyl group, cycloheptylmethyl group and cyclooctylmethyl group. In the C₁ -C₆ alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents, examples of the substituents which may substitute on the benzene ring include, for example, alkyl groups such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, and n-octyl group; alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, n-hexyloxy group, n-heptyloxy group, and n-octyloxy group; and halogen atoms such as fluorine atom, chlorine atom, bromine atom, and iodine atom. Examples of the C₁ -C₆ alkyl group substituted with one ore more phenyl groups include, for example, benzyl group, phenethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylpentyl group and 6-phenylhexyl group.

Specific examples of the compounds according to the present invention include the following compounds. However, the present invention is not limited to these examples.

(1) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

(2) 4-[4-[1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric acid

(3) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

(4) 4-[4-[1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric acid

(5) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)butyl]phenyl]butyrate

(6) 4-[4-[1-(4-chlorophenylsulfonylamino)butyl]phenyl]butyric acid

(7) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)pentyl]phenyl]butyrate

(8) 4-[4-[1-(4-chlorophenylsulfonylamino)pentyl]phenyl]butyric acid

(9) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyrate

(10) ethyl 4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyrate

(11) 4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid

(12) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)heptyl]phenyl]butyrate

(13) 4-[4-[1-(4-chlorophenylsulfonylamino)heptyl]phenyl]butyric acid

(14) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)octyl]phenyl]butyrate

(15) 4-[4-[1-(4-chlorophenylsulfonylamino)octyl]phenyl]butyric acid

(16) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)nonyl]phenyl]butyrate

(17) 4-[4-[1-(4-chlorophenylsulfonylamino)nonyl]phenyl]butyric acid

(18) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)decyl]phenyl]butyrate

(19) 4-[4-[1-(4-chlorophenylsulfonylamino)decyl]phenyl]butyric acid

(20) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyrate

(21) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric acid

(22) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-methylbutyl]phenyl]butyrate

(23) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-methylbutyl]phenyl]butyric acid

(24) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-4-methylpentyl]phenyl]butyrate

(25) 4-[4-[1-(4-chlorophenylsulfonylamino)-4-methylpentyl]phenyl]butyric acid

(26) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3,3-dimethylbutyl]phenyl]butyrate

(27) 4-[4-[1-(4-chlorophenylsulfonylamino)-3,3-dimethylbutyl]phenyl]butyric acid

(28) methyl 4-[4-[(4-chlorophenylsulfonylamino)cyclopropylmethyl]phenyl]butyrate

(29) 4-[4-[(4-chlorophenylsulfonylamino)cyclopropylmethyl]phenyl]butyric acid

(30) methyl 3-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]propionate

(31) 3-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]propionic acid

(32) methyl 4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyrate

(33) ethyl 4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyrate

(34) 4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid

(35) methyl 5-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]valerate

(36) 5-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]valeric acid

(37) methyl 4-[4-[cyclopentyl(phenylsulfonylamino)methyl]phenyl]butyrate

(38) 4-[4-[cyclopentyl(phenylsulfonylamino)methyl]phenyl]butyric acid

(39) methyl 4-[4-[cyclopentyl(4-fluorophenylsulfonylamino)methyl]phenyl]butyrate

(40) 4-[4-[cyclopentyl(4-fluorophenylsulfonylamino)methyl]phenyl]butyric acid

(41) methyl 4-[4-[(4-bromophenylsulfonylamino)cyclopentylmethyl]phenyl]butyrate

(42) 4-[4-[(4-bromophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid

(43) methyl 4-[4-[cyclopentyl(p-tolylsulfonylamino)methyl]phenyl]butyrate

(44) 4-[4-[cyclopentyl(p-tolylsulfonylamino)methyl]phenyl]butyric acid

(45) methyl 4-[4-[cyclopentyl(4-methoxyphenylsulfonylamino)methyl]phenyl]butyrate

(46) 4-[4-[cyclopentyl(4-methoxyphenylsulfonylamino)methyl]phenyl]butyric acid

(47) methyl 3-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]propionate

(48) 3-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]propionic acid

(49) methyl 4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyrate

(50) 4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric acid

(51) methyl 5-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]valerate

(52) 5-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]valeric acid

(53) methyl 4-[4-[(4-chlorophenylsulfonylamino)cycloheptylmethyl]phenyl]butyrate

(54) 4-[4-[(4-chlorophenylsulfonylamino)cycloheptylmethyl]phenyl]butyric acid

(55) methyl trans-4-[4-[(4-chlorophenylsulfonylamino)(4-methylcyclohexyl)methyl]phenyl]butyrate

(56) trans-4-[4-[(4-chlorophenylsulfonylamino)(4-methylcyclohexyl)methyl]phenyl]butyric acid

(57) methyl trans-4-[4-[(4-chlorophenylsulfonylamino)(4-pentylcyclohexyl)methyl]phenyl]butyrate

(58) trans-4-[4-[(4-chlorophenylsulfonylamino)(4-pentylcyclohexyl)methyl]phenyl]butyric acid

(59) methyl trans-4-[4-[(4-chlorophenylsulfonylamino)(4-hexylcyclohexyl)methyl]phenyl]butyrate

(60) trans-4-[4-[(4-chlorophenylsulfonylamino)(4-hexylcyclohexyl)methyl]phenyl]butyric acid

(61) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclopropylethyl]phenyl]butyrate

(62) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclopropylethyl]phenyl]butyric acid

(63) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclopentylethyl]phenyl]butyrate

(64) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclopentylethyl]phenyl]butyric acid

(65) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]butyrate

(66) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]butyric acid

(67) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-cyclohexylpropyl]phenyl]butyrate

(68) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-cyclohexylpropyl]phenyl]butyric acid

(69) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-4-cyclohexylbutyl]phenyl]butyrate

(70) 4-[4-[1-(4-chlorophenylsulfonylamino)-4-cyclohexylbutyl]phenyl]butyric acid

(71) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-5-cyclohexylpentyl]phenyl]butyrate

(72) 4-[4-[1-(4-chlorophenylsulfonylamino)-5-cyclohexylpentyl]phenyl]butyric acid

(73) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-6-cyclohexylhexyl]phenyl]butyrate

(74) 4-[4-[1-(4-chlorophenylsulfonylamino)-6-cyclohexylhexyl]phenyl]butyric acid

(75) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-7-cyclohexylheptyl]phenyl]butyrate

(76) 4-[4-[1-(4-chlorophenylsulfonylamino)-7-cyclohexylheptyl]phenyl]butyric acid

(77) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cycloheptylethyl]phenyl]butyrate

(78) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-cycloheptylethyl]phenyl]butyric acid

(79) methyl 4-[4-[2-(1-adamantyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

(80) 4-[4-[2-(1-adamantyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric acid

(81) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(2-norbornyl)ethyl]phenyl]butyrate

(82) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(2-norbornyl)ethyl]phenyl]butyric acid

(83) methyl 3-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]propionate

(84) 3-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]propionic acid

(85) methyl 4-[4-[2-phenyl-1-(phenylsulfonylamino)ethyl]phenyl]butyrate

(86) 4-[4-[2-phenyl-1-(phenylsulfonylamino)ethyl]phenyl]butyric acid

(87) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(88) 4-[4-[1-(4-fluorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(89) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(90) ethyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(91) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(92) methyl 4-[4-[1-(3-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(93) 4-[4-[1-(3-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(94) methyl 4-[4-[1-(2-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(95) 4-[4-[1-(2-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(96) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(97) 4-[4-[1-(4-bromophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(98) methyl 4-[4-[1-(p-tolylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(99) 4-[4-[1-(p-tolylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(100) methyl 4-[4-[1-(4-methoxyphenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

(101) 4-[4-[1-(4-methoxyphenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(102) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]valerate

(103) 5-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]valeric acid

(104) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(2-fluorophenyl)ethyl]phenyl]butyrate

(105) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(2-fluorophenyl)ethyl]phenyl]butyric acid

(106) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyrate

(107) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyric acid

(108) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyrate

(109) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyric acid

(110) methyl 4-[4-[2-(4-chlorophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

(111) 4-[4-[2-(4-chlorophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric acid

(112) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyrate

(113) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyric acid

(114) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(4-methoxyphenyl)ethyl]phenyl]butyrate

(115) 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(4-methoxyphenyl)ethyl]phenyl]butyric acid

(116) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyrate

(117) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyric acid

(118) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-4-phenylbutyl]phenyl]butyrate

(119) 4-[4-[1-(4-chlorophenylsulfonylamino)-4-phenylbutyl]phenyl]butyric acid

(120) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-5-phenylpentyl]phenyl]butyrate

(121) 4-[4-[1-(4-chlorophenylsulfonylamino)-5-phenylpentyl]phenyl]butyric acid

(122) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-6-phenylhexyl]phenyl]butyrate

(123) 4-[4-[1-(4-chlorophenylsulfonylamino)-6-phenylhexyl]phenyl]butyric acid

(124) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-7-phenylheptyl]phenyl]butyrate

(125) 4-[4-[1-(4-chlorophenylsulfonylamino)-7-phenylheptyl]phenyl]butyric acid

(126) methyl 4-[4-[3-(4-butylphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

(127) 4-[4-[3-(4-butylphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric acid

(128) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-pentylphenyl)propyl]phenyl]butyrate

(129) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-pentylphenyl)propyl]phenyl]butyric acid

(130) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-hexylphenyl)propyl]phenyl]butyrate

(131) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-hexylphenyl)propyl]phenyl]butyric acid

(132) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-heptylphenyl)propyl]phenyl]butyrate

(133) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-heptylphenyl)propyl]phenyl]butyric acid

(134) methyl 4-[4-[3-(4-butoxyphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

(135) 4-[4-[3-(4-butoxyphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric acid

(136) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-pentyloxyphenyl)propyl]phenyl]butyrate

(137) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-pentyloxyphenyl)propyl]phenyl]butyric acid

(138) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-hexyloxyphenyl)propyl]phenyl]butyrate

(139) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-hexyloxyphenyl)propyl]phenyl]butyric acid

(140) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(o-tolyl)propyl]phenyl]butyrate

(141) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(o-tolyl)propyl]phenyl]butyric acid

(142) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(m-tolyl)propyl]phenyl]butyrate

(143) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(m-tolyl)propyl]phenyl]butyric acid

(144) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(p-tolyl)propyl]phenyl]butyrate

(145) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(p-tolyl)propyl]phenyl]butyric acid

(146) methyl 4-[4-[3-(4-cholorophenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

(147) 4-[4-[3-(4-cholorophenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric acid

(148) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-fluorophenyl)propyl]phenyl]butyrate

(149) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-fluorophenyl)propyl]phenyl]butyric acid

(150) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-methoxyphenyl)propyl]phenyl]butyrate

(151) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(4-methoxyphenyl)propyl]phenyl]butyric acid

(152) (+)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric acid

(153) (-)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric acid

(154) (+)-4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid

(155) (-)-4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid

(156) (+)-4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric acid

(157) (-)-4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric acid

(158) (+)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(159) (-)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid

(160) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)pentyl]phenyl]valerate

(161) 5-[4-[1-(4-chlorophenylsulfonylamino)pentyl]phenyl]valeric acid

(162) methyl 4-[4-[1-(phenylsulfonylamino)hexyl]phenyl]butyrate

(163) 4-[4-[1-(phenylsulfonylamino)hexyl]phenyl]butyric acid

(164) methyl 4-[4-[1-(4-bromophenylsulfonylamino)hexyl]phenyl]butyrate

(165) 4-[4-[1-(4-bromophenylsulfonylamino)hexyl]phenyl]butyric acid

(166) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)hexyl]phenyl]butyrate

(167) 4-[4-[1-(4-fluorophenylsulfonylamino)hexyl]phenyl]butyric acid

(168) methyl 4-[4-[1-(p-tolylsulfonylamino)hexyl]phenyl]butyrate

(169) 4-[4-[1-(p-tolylsulfonylamino)hexyl]phenyl]butyric acid

(170) methyl 4-[4-[1-(4-methoxyphenylsulfonylamino)hexyl]phenyl]butyrate

(171) 4-[4-[1-(4-methoxyphenylsulfonylamino)hexyl]phenyl]butyric acid

(172) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]valerate

(173) 5-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]valeric acid

(174) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-4-methylpentyl]phenyl]valerate

(175) 5-[4-[1-(4-chlorophenylsulfonylamino)-4-methylpentyl]phenyl]valeric acid

(176) methyl 4-[4-[5-methyl-1-(phenylsulfonylamino)hexyl]phenyl]butyrate

(177) 4-[4-[5-methyl-1-(phenylsulfonylamino)hexyl]phenyl]butyric acid

(178) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-5-methylhexyl]phenyl]butyrate

(179) 4-[4-[1-(4-chlorophenylsulfonylamino)-5-methylhexyl]phenyl]butyric acid

(180) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-5-methylhexyl]phenyl]butyrate

(181) 4-[4-[1-(4-bromophenylsulfonylamino)-5-methylhexyl]phenyl]butyric acid

(182) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-5-methylhexyl]phenyl]butyrate

(183) 4-[4-[1-(4-fluorophenylsulfonylamino)-5-methylhexyl]phenyl]butyric acid

(184) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-5-methylhexyl]phenyl]valerate

(185) 5-[4-[1-(4-chlorophenylsulfonylamino)-5-methylhexyl]phenyl]valeric acid

(186) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-6-methylheptyl]phenyl]butyrate

(187) 4-[4-[1-(4-chlorophenylsulfonylamino)-6-methylheptyl]phenyl]butyric acid

(188) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyrate

(189) 4-[4-[1-(4-chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyric acid

(190) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]valerate

(191) 5-[4-[1-(4-chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]valeric acid

(192) methyl 4-[4-[5,5-dimethyl-1-(phenylsulfonylamino)hexyl]phenyl]butyrate

(193) 4-[4-[5,5-dimethyl-1-(phenylsulfonylamino)hexyl]phenyl]butyric acid

(194) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyrate

(195) 4-[4-[1-(4-chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyric acid

(196) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyrate

(197) 4-[4-[1-(4-bromophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyric acid

(198) methyl 4-[4-[5,5-dimethyl-1-(4-fluorophenylsulfonylamino)hexyl]phenyl]butyrate

(199) 4-[4-[5,5-dimethyl-1-(4-fluorophenylsulfonylamino)hexyl]phenyl]butyric acid

(200) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]valerate

(201) 5-[4-[1-(4-chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]valeric acid

(202) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyrate

(203) 4-[4-[1-(4-chlorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyric acid

(204) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-cyclopentylpropyl]phenyl]butyrate

(205) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-cyclopentylpropyl]phenyl]butyric acid

(206) methyl 5-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]valerate

(207) 5-[4-[1-(4-chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]valeric acid

(208) methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(3-fluorophenyl)propyl]phenyl]butyrate

(209) 4-[4-[1-(4-chlorophenylsulfonylamino)-3-(3-fluorophenyl)propyl]phenyl]butyric acid

(210) (+)-4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid

(211) (-)-4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid

(212) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)pentyl]phenyl]butyrate

(213) 4-[4-[1-(4-fluorophenylsulfonylamino)pentyl]phenyl]butyric acid

(214) methyl 4-[4-[1-(4-bromophenylsulfonylamino)pentyl]phenyl]butyrate

(215) 4-[4-[1-(4-bromophenylsulfonylamino)pentyl]phenyl]butyric acid

(216) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)heptyl]phenyl]butyrate

(217) 4-[4-[1-(4-fluorophenylsulfonylamino)heptyl]phenyl]butyric acid

(218) methyl 4-[4-[1-(4-bromophenylsulfonylamino)heptyl]phenyl]butyrate

(219) 4-[4-[1-(4-bromophenylsulfonylamino)heptyl]phenyl]butyric acid

(220) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-4-methylpentyl]phenyl]butyrate

(221) 4-[4-[1-(4-fluorophenylsulfonylamino)-4-methylpentyl]phenyl]butyric acid

(222) methyl 4-[4-[1-(4-bromophenylsulfonylamino) -4-methylpentyl]phenyl]butyrate

(223) 4-[4-[1-(4-bromophenylsulfonylamino)-4-methylpentyl]phenyl]butyric acid

(224) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-6-methylheptyl]phenyl]butyrate

(225) 4-[4-[1-(4-fluorophenylsulfonylamino)-6-methylheptyl]phenyl]butyric acid

(226) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-6-methylheptyl]phenyl]butyrate

(227) 4-[4-[1-(4-bromophenylsulfonylamino)-6-methylheptyl]phenyl]butyric acid

(228) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyrate

(229) 4-[4-[1-(4-fluorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyric acid

(230) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyrate

(231) 4-[4-[1-(4-bromophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyric acid

(232) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyrate

(233) 4-[4-[1-(4-fluorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyric acid

(234) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyrate

(235) 4-[4-[1-(4-bromophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyric acid

(236) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyrate

(237) 4-[4-[1-(4-bromophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyric acid

(238) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyrate

(239) 4-[4-[1-(4-bromophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyric acid

(240) methyl 4-[4-[2-(4-chlorophenyl)-1-(4-fluorophenylsulfonylamino)ethyl]phenyl]butyrate

(241) 4-[4-[2-(4-chlorophenyl)-1-(4-fluorophenylsulfonylamino)ethyl]phenyl]butyric acid

(242) methyl 4-[4-[2-(4-chlorophenyl)-1-(4-bromophenylsulfonylamino)ethyl]phenyl]butyrate

(243) 4-[4-[2-(4-chlorophenyl)-1-(4-bromophenylsulfonylamino)ethyl]phenyl]butyric acid

(244) methyl 4-[4-[2-(4-bromophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

(245) 4-[4-[2-(4-bromophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric acid

(246) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyrate

(247) 4-[4-[1-(4-fluorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyric acid

(248) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyrate

(249) 4-[4-[1-(4-bromophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyric acid

(250) methyl 4-[4-[1-(4-fluorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyrate

(251) 4-[4-[1-(4-fluorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyric acid

(252) methyl 4-[4-[1-(4-bromophenylsulfonylamino)-3-phenylpropyl]phenyl]butyrate

(253) 4-[4-[1-(4-bromophenylsulfonylamino)-3-phenylpropyl]phenyl]butyric acid

Among these compounds, preferred compounds are Compound Nos. 7-13, 24, 25, 87-91, 96, 97, 106-113, 116, 117, 164-167, 178, 179, 186-189, 194, 195, 202, and 203. Particularly preferred compounds are Compound Nos. 8, 11, 91, 97, 107, 111, 113, 165, 167, 179, and 187.

Among the aforementioned compounds of the present invention represented by general Formula (I), the compounds wherein R³ is a hydrogen atom may optionally be converted into pharmacologically acceptable salts, and the resulting salts may further be converted into free acids.

Examples of the pharmaceutically acceptable salts of the aforementioned compounds of the present invention represented by the general Formula (I) include alkali addition salts. Examples include inorganic alkali salts such as sodium, potassium, calcium, and ammonium salts or salts of organic bases such as trimethylamine, triethylamine, pyrrolidine, piperidine, piperazine, and N-methylmorpholine.

The compounds of the present invention represented by the above-described Formula (I) may exist as optical isomers or stereoisomers due to asymmetric carbon atoms. These isomers as well as their mixtures fall within the scope of the present invention.

The novel benzenesulfonamide derivatives of the present invention represented by the above-described general Formula (I) may be prepared by the methods set out below. However, processes for preparing the compounds are not limited to these methods.

According to the first embodiment of the methods for preparing the compounds of the present invention, the compounds represented by the above-described general Formula (I) can be prepared by reacting an amine derivative represented by the following general Formula (II): ##STR5## wherein R², R³ and n are the same as those set out above with a sulfonyl chloride derivative represented by the following general Formula (III): ##STR6## wherein R¹ is the same as that set out above, in a solvent in the presence of a base, and optionally hydrolyzing its ester group.

Any solvents may be used to react the compounds of the general Formula (II) with the compounds of the general Formula (III) so far that they do not affect the reaction. Examples include etheric solvents such as diethyl ether, tetrahydrofuran and 1,4-dioxane; halogenated hydrocarbonic solvents such as chloroform, methylene chloride and 1,2-dichloroethane; aromatic hydrocarbonic solvents such as benzene and toluene; aprotic polar solvents such as acetonitrile, N,N-dimethylformamide and dimethyl sulfoxide.

Examples of the base used for the reaction include, for example, organic bases such as triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and pyridine, and inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate. The reaction may be carried out at a temperature of from 0° C. to the reflux temperature of a solvent. In addition, the hydrolysis reaction of the ester may be carried out by using a base or an acid in an aqueous solvent.

The solvent used for the reaction may be water alone. However, it is preferable to use water mixed with a solvent such as methanol, ethanol, n-propanol, isopropanol, n-butanol, acetone, tetrahydrofuran and 1,4-dioxane.

Examples of the base used for this reaction include sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, and examples of the acid include hydrochloric acid, hydrobromic acid and sulfuric acid. The reaction may be carried out at a temperature of from 0° C. to the reflux temperature of a solvent.

The amine derivatives represented by the above-described general Formula (II) used as starting materials in the present process for preparation are novel compounds and may be prepared, for example, according to the following processes. The details are shown as References in Examples. ##STR7## (In the above scheme, , R², R³ and n are the same as those set out above.)

According to the second embodiment for preparing the compounds of the present invention, the compounds represented by the above-described general Formula (I) wherein R³ is a hydrogen atom can be converted to their (+)- or (-)-optical isomers by treating racemates with optically active bases to form their salts and subjecting the salts to fractional crystallizations.

For example, quinidine, hydroquinidine, quinine, brucine, cinchonidine, cinchonine, ephedrine, (S)-(-)-1-phenylethylamine, (R)-(+)-1-phenylethylamine, (R)-(-)-2-amino-1-butanol, (S)-(+)-2-amino-1-butanol, (1R,2S)-(-)-2-amino-1,2-diphenylethanol, (1S,2R)-(+)-2-amino-1,2-diphenylethanol, (-)-cis-2-benzylaminocyclohexanemethanol, (+)-cis-2-benzylaminocyclohexanemethanol, (R)-(+)-1-(p-tolyl)ethylamine, (S)-(-)-1-(p-tolyl)ethylamine, (S)-(+)-α-methyl-4-nitrobenzylamine, (R)-(-)-α-methyl-4-nitrobenzylamine, (S)-(-)-1-(1-naphthyl)ethylamine, (R)-(+)-1-(1-naphthyl)ethylamine, L-phenylalaninol, L-(+)-lysine, L-(+)-arginine may be used as the optically active base used for the present preparation method.

Examples of the solvent used for the optical resolution include, for example, water; lower alcoholic solvents such as methanol, ethanol and isopropanol; halogenated hydrocarbonic solvents such as chloroform, dichloromethane, dichloroethane and carbon tetrachloride; ketone solvents such as acetone and methyl ethyl ketone; etheric solvents such as ether, diisopropyl ether and dioxane; aromatic hydrocarbonic solvents such as benzene, toluene and xylene; saturated hydrocarbonic solvents such as hexane, pentane and cyclohexane; nitrile solvents such as acetonitrile; ester solvents such as ethyl acetate and ethyl formate; amide solvents such as N,N-dimethylformamide and N,N-dimethylacetamide; organic solvents such as dimethyl sulfoxide and nitromethane; and mixtures thereof. The treatment with the optically active base may be carried out at from 0° C. to a temperature under slight heating.

Pharmaceutical compositions comprising as an active ingredient the novel benzenesulfonamide derivatives represented by the above-described general Formula (I) or pharmaceutically acceptable salts thereof thus prepared may be manufactured in the forms of orally administrable formulations such as capsules, tablets, subtilized granules, granules, powders and syrups, or injections for administrations to patients. These pharmaceutical compositions may be prepared in a conventional manner by adding pharmacologically and pharmaceutically acceptable additives. More specifically, for orally administrable formulations, pharmaceutical ingredients such as, for example, excipients such as lactose, D-mannitol, corn starch and crystalline cellulose; disintegrators such as carboxymethylcellulose and calcium carboxymethylcellulose; binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose and polyvinylpyrrolidone; lubricants such as magnesium stearate and talc; and coating agents such as hydroxypropylmethylcellulose, saccharose and titanium oxide may be used. For injections, solubilizers or dissolving agents for preparing formulations in the form of aqueous compositions or compositions dissolved upon use such as distilled water for injections, physiological saline and propylene glycol; pH adjusting agents such as inorganic or organic acids and bases; isotonic agents such as sodium chloride, glucose and glycerin; and stabilizers may be used.

Dose of the compounds of the present invention for a patient to be treated may generally be about from 1 to 1,000 mg for oral administration and about from 1 to 500 mg for parenteral administration per day for an adult patient, which may depend on the conditions of the patient.

Pharmacological Action

As examples of excellent pharmacological actions exhibited by the compounds of the present invention, each of test results relating to thromboxane A₂ antagonistic effect, inhibitory effect on broncho-constriction, inhibitory effect on thromboxane A₂ synthetase, and leukotriene D₄ antagonistic effect will be set out below.

Daltroban was used as a reference drug.

Experiment 1: Thromboxane A₂ antagonistic effect

Blood was collected from the abdominal aorta of guinea-pigs (about 400 g wt.) into 1/10 volume of 3.8% sodium citrate, and then platelet-rich plasma (PRP: 6×10⁵ cells/μl) was obtained by centrifugation. A cuvette was filled with PRP 190 μl and set in an aggregometer (Hema Tracer I; Niko Bioscience). Incubation was carried out for 2 min. at 37° C. after the addition of 1 μl of dimethyl sulfoxide solution of test compounds. To the PRP, 10 μl of U-46619 (Cayman), a thromboxane A₂ /prostaglandin H₂ receptor agonist and potent platelet aggregation inducer, was added at the final concentration of 2 μg/ml, and platelet aggregation was measured by an aggregometer. IC₅₀ values (concentrations which produced 50% inhibition against platelet aggregation) are shown in Table 1.

                  TABLE 1     ______________________________________     Thromboxane A.sub.2 receptor antagonistic effect     Test compound               IC.sub.50 (μM)                         Test compound  IC.sub.50 (μM)     ______________________________________     Example 62               0.050     Example 89     0.032     Example 64               0.16      Example 90     0.32     Example 66               0.32      Example 91     0.32     Example 67               0.40      Example 92     0.32     Example 69               0.20      Example 93     0.32     Example 70               0.32      Example 94     0.063     Example 71               0.40      Example 95     0.16     Example 72               0.32      Example 96     0.63     Example 73               0.25      Example 97     0.32     Example 74               0.32      Example 98     0.32     Example 75               0.32      Example 99     0.32     Example 78               0.32      Example 100    0.79     Example 79               0.32      Example 107    0.25     Example 80               1.0       Example 108    0.50     Example 82               0.40      Example 113    0.40     Example 85               0.40      Example 114    0.32     Example 86               0.25      Example 115    0.32     Example 87               0.32      Example 116    0.50     Example 88               0.32      Reference compound                                        2.0     ______________________________________

The compounds of the present invention exhibited higher antagonistic effect on thromboxane A₂ receptor compared to the reference compound.

Experiment 2: Inhibitory effect on broncho-constriction induced by U-46619

Airway resistance was evaluated according to the method of Konzett-Roessler [Naunyn-Schmiedberg's Arch. Exp. Path. Pharmak., Vol. 195, 71 (1940)]. Male hartley guinea-pigs (about 400 g wt.) were anesthetized with urethane (1.5 g/kg, i.p.) and ventilated by an artificial respirator (Model 683; Harvard). At that time, overflowed air volume above the pressure of about 12 cm H₂ O was measured by using a sensor (Model 7020; Ugo basile) and the value was used as an index of broncho-constriction. 0.3 mg/kg (5 ml/kg) of test compounds suspended in 5% gum Arabic was administered orally to Guinea-pigs fasted beforehand for 24 hr. After 2 hrs, U-46619 (4 μg/kg; Cayman) was administered through the cervical vein, and then maximal response was measured. Inhibitory rates compared to the reference group were calculated based on the response rate normalized by the complete closure as 100%. The results are shown in Table 2.

                  TABLE 2     ______________________________________     Inhibitory effect on broncho-constriction induced by U-46619               Inhibition               Inhibition     Test compound               rate (%)  Test compound  rate (%)     ______________________________________     Example 66               85        Example 97     88     Example 67               86        Example 98     84     Example 79               55        Reference compound                                        18     Example 96               89     ______________________________________

The compounds of the present invention exhibited higher inhibitory effects on the broncho-constriction induced by U-46619 compared to the reference compound.

Experiment 3: Inhibitory effect on thromboxane A₂ synthetase

100 μg/ml (285 μl) of the commercially available human platelet membrane fraction (RAN) as a source of thromboxane A₂ synthetase, dimethyl sulfoxide solution of test compounds (10 μl) and 100 μg/ml (5 μl) of prostaglandin H₂ (Cayman) were mixed and reaction was carried out for 3 min at 25° C. Amount of thromboxane B₂, a stable metabolite derived from thromboxane A₂ produced, was measured by RIA method (TXB₂ quantification kit; NEN). Concentrations which produce 50% inhibition of the enzyme activity (IC₅₀ values) are shown in Table 3.

                  TABLE 3     ______________________________________     Inhibitory effect on thromboxane A.sub.2 synthetase     Test compound               IC.sub.50 (μM)                          Test compound                                      IC.sub.50 (μM)     ______________________________________     Example 62               4.0        Example 73  1.6     Example 63               2.0        Example 74  3.2     Example 69               2.0        Reference   40                          compound     ______________________________________

The compounds of the present invention exhibited higher inhibitory effects on thromboxane A₂ synthetase compared to the reference compound.

Experiment 4: Leukotriene D₄ antagonistic effect

According to an ordinary method, tracheas were isolated from male Hartley guinea-pigs, and ring specimens of approximately 2 cm length were prepared. These specimens were suspended isotonically in organ baths that contained Krebs solution at 37° C. under a resting tension of 0.5 g. After repeated contractions with acetylcholine (1×10⁻⁶ M; Ovisot for injection, Daiichi Seiyaku), and the first concentration-response curves was obtained by cummulative applications of leukotriene D₄ (ULTRA FINE) into the organ baths. After treatments with test compounds at adequate concentrations for 30 min, the second concentration-response curves were obtained in the same manner as first applications. pK_(B) values were calculated using these two concentration-response curves according to the method of Schild [Pharmacological Review, Vol. 9, 242 (1957)]. Indomethacin (3×10⁻⁶ M; Sigma) was added beforehand to the organ bath to eliminate possible affections by thromboxane A₂ and prostaglandin produced by stimulus of leukotriene D₄ [Japan J. Pharmacol., Vol. 60, 227 (1992)]. The results are shown in Table 4.

                  TABLE 4     ______________________________________     Leukotriene D.sub.4 antagonistic effect     Test compound                 pK.sub.B Test compound  pK.sub.B     ______________________________________     Example 66  6.1      Example 96     6.0     Example 67  6.7      Example 97     5.9     Example 71  6.7      Example 98     6.4     Example 74  6.3      Example 99     6.9     Example 75  6.4      Example 102    6.7     Example 76  6.7      Example 106    6.9     Example 77  6.2      Example 107    7.0     Example 78  6.0      Example 108    6.8     Example 79  7.0      Example 113    7.4     Example 80  6.9      Example 116    6.7     Example 84  6.7      Example 117    6.6     Example 85  6.8      Reference compound                                         <4     Example 95  6.3     ______________________________________

The reference compound was inactive in leukotriene D₄ antagonistic effect. On the other hand, the compounds of the present invention exhibited excellent leukotriene D₄ antagonistic effects.

Experiment 5: Inhibitory effect on broncho-constriction induced by leukotriene D₄

Airway resistance was evaluated according to the method of Konzett-Roessler [Naunyn-Schmiedberg's Arch. Exp. Path. Pharmak., Vol. 195, 71 (1940)]. After male Hartley guinea-pig fasted beforehand for 24 hr were anesthetized with urethane, overflowed air volume was measured under artificial ventilation as an index of broncho-constriction. 30 mg/kg (5 ml/kg) of test compounds suspended in 5% gum Arabic were administered orally to the rats. Leukotriene D₄ (1 μg/kg; ULTRA FINE) was administered through the cervical vein after 2 hr, and then values were measured at 2 min after the time when responses became maximum. Inhibitory rates compared to the control group were calculated based on the response rate normalized by the overflowed volume at complete closure as 100% broncho-constriction state. The results are shown in Table 5. Indomethacin (2 mg/kg, i.v.) and propranolol (1 mg/kg, i.v.) were administered at 10 min and 5 min before the administration of leukotriene D₄, respectively.

                  TABLE 5     ______________________________________     Inhibitory effect on broncho-constriction     induced by leukotriene D.sub.4               Inhibition               Inhibition     Test compound               rate (%)  Test compound  rate (%)     ______________________________________     Example 66               81        Example 102    50     Example 67               80        Example 104    83     Example 71               68        Example 105    82     Example 80               60        Example 106    58     Example 96               43        Example 107    83     Example 97               56        Example 108    82     Example 98               57        Reference compound                                        ≦0     Example 99               64     ______________________________________

The reference compound exhibit no inhibitory effect on broncho-constriction induced by leukotriene D₄. On the other hand, the compounds of the present invention exhibited potent inhibitory effects on leukotriene D₄ -induced bronchoconstriction.

EXAMPLES

The present invention will be further illustrated by the following References and Examples. However, the present invention is not limited to any specific details described in these examples.

Reference Example 1 Methyl 4-[4-(Phenylacetyl)phenyl]butyrate

To a solution of 25.0 g of methyl 4-phenylbutyrate in 100 ml of carbon disulfide, 37.3 g of anhydrous aluminium chloride was added and then a solution of 43.3 g of phenylacetyl chloride in 25 ml of carbon disulfide was added dropwise, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice-water and extracted with methylene chloride. The methylene chloride layer was washed with aqueous potassium carbonate solution, dried, and then the solvent was removed. The residue was purified by column chromatography on silica gel (methylene chloride:n-hexane=2:1→methylene chloride) to afford 27.3 g of colorless crystals. Recrystallization from isopropyl ether gave colorless flakes, mp 54°˜54.5° C.

Analysis for C₁₉ H₂₀ O₃

Calculated C, 77.00; H, 6.80 Found C, 77.03; H, 6.80

Reference Example 2 Methyl 3-[4-(Phenylacetyl)phenyl]propionate

To a solution of 1.00 g of methyl 3-phenylpropionate in 6 ml of carbon disulfide, 1.62 g of anhydrous aluminium chloride was added under ice-cooling, and then 0.94 g of phenylacetyl chloride was added dropwise and stirring was continued at room temperature for 6 hours. The reaction mixture was poured into ice-water and extracted with methylene chloride. The methylene chloride layer was washed successively with water, aqueous potassium carbonate solution and water, dried, and then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:n-hexane=2:1) to afford 1.05 g of colorless crystals. Recrystallization from isopropyl ether gave colorless flakes, mp 77°˜78° C.

Analysis for C₁₈ H₁₈ O₃

Calculated C, 76.57; H, 6.43 Found C, 76.59; H, 6.47

Reference Example 3 Methyl 5-[4-(Phenylacetyl)phenyl]valerate

To a solution of 5.12 g of methyl 5-phenylvalerate in 25 ml of carbon disulfide, 7.10 g of anhydrous aluminium chloride was added under ice-cooling, and then 4.11 g of phenylacetyl chloride was added dropwise and stirring was continued at room temperature for 6 hours. The reaction mixture was poured into ice-water and extracted with methylene chloride. The methylene chloride layer was washed successively with water, aqueous potassium carbonate solution and water, dried, and then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:n-hexane=2:1) to afford 5.45 g of colorless crystals. Recrystallization from isopropyl ether gave colorless flakes, mp 53.5°˜54° C.

Analysis for C₂₀ H₂₂ O₃

Calculated C, 77.39; H, 7.14 Found C, 77.68; H, 7.24

The compounds of Reference Examples 4 through 42 shown in Tables 6 to 12 were obtained in the same manner as described in Reference Examples 1 to 3.

                                      TABLE 6     __________________________________________________________________________     Reference                       Analysis     Example                         (upper:Calculated)     No.   Compound    Appearance                              mp     (lower:Found)     __________________________________________________________________________     4     Methyl 4-[4-[(2-Fluoro-                       colorless                              53˜54° C.                                     C.sub.19 H.sub.19 FO.sub.3           phenyl)acetyl]phenyl]-                       needles       C, 72.60; H, 6.09           butyrate    (i-Pr.sub.2 O)                                     C, 72.59; H, 6.07     5     Methyl 4-[4-[(3-Fluoro-                       colorless                              49˜51° C.                                     C.sub.19 H.sub.19 FO.sub.3           phenyl)acetyl]phenyl]-                       flakes        C, 72.60; H, 6.09           butyrate    (i-Pr.sub.2 O)                                     C, 72.72; H, 6.06     6     Methyl 4-[4-[(4-Fluoro-                       colorless                              84˜86° C.                                     C.sub.19 H.sub.19 FO.sub.3           phenyl)acetyl]phenyl]-                       needles       C, 72.60; H, 6.09           butyrate    (i-Pr.sub.2 O)                                     C, 72.62; H, 6.19     7     Methyl 4-[4-[(4-Chloro-                       colorless                              103˜105° C.                                     C.sub.19 H.sub.19 ClO.sub.3           phenyl)acetyl]phenyl]-                       needles       C, 68.98; H, 5.79           butyrate    (i-Pr.sub.2 O)                                     C, 69.13; H, 5.88     8     Methyl 4-[4-[(p-Tolyl)-                       colorless                              62.5˜63° C.                                     C.sub.20 H.sub.22 O.sub.3           acetyl]phenyl]-                       flakes        C, 77.39; H, 7.14           butyrate    (i-Pr.sub.2 O)                                     C, 77.37; H, 7.36     9     Methyl 4-(4-Decanoyl-                       colorless                              47.5˜48.5° C.                                     C.sub.21 H.sub.32 O.sub.3           phenyl)butyrate                       needles       C, 75.86; H, 9.70                       (n-Hexane)    C, 75.83; H, 9.98     10    Methyl 4-[4-(6-Cyclo-                       colorless                              42.5˜44° C.                                     C.sub.23 H.sub.34 O.sub.3           hexylhexanoyl)phenyl]-                       crystals      C, 77.05; H, 9.56           butyrate    (MeOH)        C, 77.04; H, 9.72     __________________________________________________________________________

                                      TABLE 7     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     11    Methyl 4-(4-Acetylphenyl)-                         1738, 1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=           butyrate      1684  7.5Hz), 2.59(3H, s), 2.72(2H, t, J=7.5Hz),           pale brown oil      3.67(3H, s), 7.27(2H, d, J=8Hz),                               7.89(2H, d, J=8Hz)     12    Methyl 4-(4-Propionyl-                         1738, 1.22(3H, t, J=7.5Hz), 1.98(2H, qn, J=           phenyl)butyrate                         1688  7.5Hz), 2.34(2H, t, J=7.5Hz), 2.71(2           pale yellow oil     H, t, J=7.5Hz), 2.98(2H, q, J=7.5Hz),                               3.67(3H, s), 7.26(2H, d, J=8.5Hz), 7.89(2H,                               d, J=8.5Hz)     13    Methyl 4-(4-Butyryl-                         1738, 1.00(3H, t, J=7.5Hz), 1.77(2H, sex, J=7.5Hz),           phenyl)butyrate                         1686  1.98(2H, qn, J=7.5Hz), 2.34(2H,           colorless oil       t, J=7.5Hz), 2.71(2H, t, J=7.5Hz),           bp 148˜151° C. (2 mmHg)                               2.92(2H, t, J=7.5Hz), 3.67(3H, s),                               7.26(2H, d, J=8Hz), 7.89(2H, d, J=8Hz)     14    Methyl 4-(4-Pentanoyl-                         1738, 0.95(3H, t, J=7.5Hz), 1.41(2H, sex, J=           phenyl)butyrate                         1686  7.5Hz), 1.72(2H, qn, J=7.5Hz), 1.98(2H,           pale reddish brown oil                               qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),                               2.71(2H, t, J=7.5Hz), 2.94(2H, t,                               J=7.5Hz), 3.67(3H, s), 7.26(2H, d, J=                               8Hz), 7.89(2H, d, J=8Hz)     15    Methyl 4-(4-Hexanoyl-                         1738, 0.91(3H, t, J=7Hz), 1.32-1.41(4H, m),           phenyl)butyrate                         1684  1.69-1.78(2H, m), 1.98(2H, qn, J=7.5Hz),           colorless oil       2.34(2H, t, J=7.5Hz), 2.71(2H,                               t, J=7.5Hz), 2.93(2H, t, J=7.5Hz), 3.67                               (3H, s), 7.26(2H, d, J=8Hz), 7.89(2H,                               d, J=8Hz)     16    Methyl 4-(4-Isovaleryl-                         1738, 0.99(6H, d, J=7Hz), 1.98(2H, qn, J=7.5Hz),           phenyl)butyrate                         1684  2.28-2.32(1H, m), 2.34(2H, t, J=7.5Hz),           colorless oil       2.71(2H, t, J=7.5Hz), 2.81(2H,                               d, J=7Hz), 3.67(3H, s), 7.26(2H, d,                               J=8Hz), 7.88(2H, d, J=8Hz)     17    Methyl 4-[4-(4-Methyl-                         1738, 0.95(6H, d, J=6Hz), 1.60-1.69(3H, m),           pentanoyl)phenyl]butyrate                         1686  1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),           colorless oil       2.71(2H, t, J=7.5Hz), 2.94(2H,                               t, J=7.5Hz), 3.67(3H, s), 7.27(2H,                               d, J=8Hz), 7.89(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 8     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     18    Methyl 4-[4-(3,3-Dimethyl-                         1738, 1.06(9H, s), 1.98(2H, qn, J=7.5Hz), 2.34(2H,           butyryl)phenyl]butyrate                         1688, t, J=7.5Hz), 2.71(2H, t, J=7.5Hz),           colorless oil 1674  2.83(2H, s), 3.67(3H, s), 7.25(2H,                               d, J=8Hz), 7.87(2H, d, J=8Hz)     19    Methyl 4-[4-(Cyclopentyl-                         1738, 1.61-1.77(4H, m), 1.88-1.93(4H, m),           carbonyl)phenyl]butyrate                         1680  1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=           yellow oil          7.5Hz), 2.71(2H, t, J=7.5Hz), 3.67(3H,                               s), 3.69(1H, qn, J=8Hz), 7.26(2H, d,                               J=8Hz), 7.90(2H, d, J=8Hz)     20    Methyl 4-[4-(Cyclohexyl-                         1738, 1.22-1.32(1H, m), 1.34-1.54(4H, m),           carbonyl)phenyl]butyrate                         1682  1.70-1.76(1H, m), 1.81-1.91(4H, m),           colorless oil       1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=                               7.5Hz), 2.71(2H, t, J=7.5Hz), 3.20-3.28(1H,                               m), 3.67(3H, s), 7.26(2H, d, J=8Hz),                               7.87(2H, d, J=8Hz)     21    Methyl 4-[4-(Cycloheptyl-                         1738, 1.50-1.75(8H, m), 1.75-1.84(2H, m),           carbonyl)phenyl]butyrate                         1682  1.87-1.95(2H, m), 1.98(2H, qn, J=7.5Hz),           pale brown oil      2.34(2H, t, J=7.5Hz), 2.71(2H, t,                               J=7.5Hz), 3.37-3.45(1H, m), 3.67(3H,                               s), 7.26(2H, d, J=8Hz), 7.86(2H, d,                               J=8Hz)     22    Methyl 4-[4-(Cyclopentyl-                         1738, 1.16-1.22(2H, m), 1.54-1.58(2H, m),           acetyl)phenyl]butyrate                         1684  1.63-1.66(2H, m), 1.86-1.91(2H, m),           colorless oil       1.98(2H, qn, J=7.5Hz), 2.32-2.41(1H,                               m), 2.34(2H, t, J=7.5Hz), 2.71(2H, t,                               J=7.5Hz), 2.96(2H, d, J=7Hz), 3.67(3H,                               s), 7.26(2H, d, J=8Hz), 7.88(2H, d,                               J=8Hz)     23    Methyl 4-[4-(Cyclohexyl-                         1740, 0.97-1.05(2H, m), 1.15-1.20(1H, m),           acetyl)phenyl]butyrate                         1684  1.25-1.33(2H, m), 1.56-1.77(5H, m),           pale brown oil      1.93-2.02(1H, m), 1.98(2H, qn, J=7.5Hz),                               2.34(2H, t, J=7.5Hz), 2.71(2H, t,                               J=7.5Hz), 2.79(2H, d, J=7Hz), 3.67(3H,                               s), 7.26(2H, d, J=8.5Hz), 7.87(2H,                               d, J=8.5Hz)     __________________________________________________________________________

                                      TABLE 9     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     24    Methyl 4-[4-(3-Cyclohexyl-                         1738, 0.90-0.99(2H, m), 1.11-1.40(4H, m),           propionyl)phenyl]butyrate                         1686  1.58-1.81(7H, m), 1.98(2H, qn, J=7.5Hz),           colorless oil       2.34(2H, t, J=7.5Hz), 2.71(2H, t,                               J=7.5Hz), 2.95(2H, t, J=7.5Hz), 3.67(3H,                               s), 7.26(2H, d, J=8Hz), 7.88(2H,                               d, J=8Hz)     25    Methyl 4-[4-(4-Cyclohexyl-                         1738, 0.85-0.95(2H, m), 1.10-1.30(6H, m),           butyryl)phenyl]butyrate                         1686  1.02-1.77(7H, m), 1.98(2H, qn, J=7.5Hz),           pale yellow oil     2.34(2H, t, J=7.5Hz), 2.71(2H, t,                               J=7.5Hz), 2.91(2H, t, J=7.5Hz), 3.67(3H,                               s), 7.26(2H, d, J=8Hz), 7.88(2H,                               d, J=8Hz)     26    Methyl 4-[4-(5-Cyclohexyl-                         (KBr) 0.82-0.90(2H, m), 1.09-1.25(6H, m),           pentanoyl)phenyl]butyrate                         1738, 1.35-1.41(2H, m), 1.62-1.73(7H, m),           colorless needles (MeOH)                         1674  1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),           mp 50.5˜51.5° C.                               2.71(2H, t, J=7.5Hz), 2.93(2H,                               t, J=7.5Hz), 3.67(3H, s), 7.26(2H,                               d, J=8.5Hz), 7.88(2H, d, J=8.5Hz)     27    Methyl trans-4-[4-                         1738, 0.93(3H, d, J=7Hz), 1.02-1.12(2H, m),           (4-Methylcyclohexyl-                         1682  1.36-1.48(1H, m), 1.48-1.58(2H, m),           carbonyl)phenyl]butyrate                               1.79-1.86(2H, m), 1.86-1.92(2H, m),           colorless oil       1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),                               2.71(2H, t, J=7.5Hz), 3.17(1H,                               tt, J=12, 3Hz), 3.67(3H, s), 7.26(2H,                               d, J=8Hz), 7.87(2H, d, J=8Hz)     28    Methyl trans-4-[4-                         (KBr) 0.89(3H, t, J=7Hz), 0.99-1.09(2H, m),           (4-Pentylcyclohexyl-                         1734, 1.18-1.35(9H, m), 1.45-1.56(2H, m),           carbonyl)phenyl]butyrate                         1668  1.84-1.94(4H, m), 1.98(2H, qn, J=7.5Hz),           colorless needles (MeOH)                               2.34(2H, t, J=7.5Hz), 2.71(2H,           mp 62˜63° C.                               t, J=7.5Hz), 3.19(1H, tt, J=12, 3Hz),                               3.67(3H, s), 7.26(2H, d, J=8.5Hz), 7.87(2H,                               d, J=8.5Hz)     29    Methyl 4-[4-[(1-Adamantyl)-                         1738, 1.63-1.70(12H, m), 1.94-1.95(3H, m),           acetyl]phenyl]butyrate                         1672  1.98(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),           pale yellow oil     2.69(3H, s), 2.71(2H, t, J=7.5Hz),                               3.67(3H, s), 7.25(2H, d, J=8Hz),                               7.87(2, H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 10     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     30    Methyl 4-[4-[(2-Norbornyl)-                         1738, 1.07-1.59(8H, m), 1.98(2H, qn, J=7.5Hz),           acetyl]phenyl]butyrate                         1684  2.01-2.08(2H, m), 2.23(1H, s), 2.34(2H,           pale brown oil      t, J=7.5Hz), 2.71(2H, t, J=7.5Hz),                               2.76(1H, dd, J=16, 7Hz), 2.94(1H,                               dd, J=16, 7Hz), 3.67(3H, s), 7.26(2H,                               d, J=8Hz), 7.87(2H, d, J=8Hz)     31    Methyl 5-(4-Pentanoyl-                         1738, 0.95(3H, t, J=7.5Hz), 1.41(2H, sex, J=7.5Hz),           phenyl)valerate                         1684  1.64-1.75(6H, m), 2.30-2.38(2H,           colorless oil       m), 2.64-2.73(2H, m), 2.94(2H,                               t, J=7.5Hz), 3.67(3H, s), 7.25(2H, d,                               J=8Hz), 7.88(2H, d, J=8Hz)     32    Methyl 5-(4-Hexanoyl-                         1740, 0.91(3H, t, J=7Hz), 1.32-1.40(4H, m),           phenyl)valerate                         1684  1.62-1.77(6H, m), 2.31-2.36(2H, m),           colorless oil       2.62-2.73(2H, m), 2.93(2H, t, J=7.5Hz),                               3.66(3H, s), 7.25(2H, d, J=8Hz),                               7.88(2H, d, J=8Hz)     33    Methyl 5-[4-(Cyclohexyl-                         1738, 0.96-1.05(2H, m), 1.11-1.22(1H, m),           acetyl)phenyl]valerate                         1684  1.23-1.34(2H, m), 1.60-1.80(9H, m),           pale brown oil      1.92-2.02(1H, m), 2.30-2.38(2H, m),                               2.65-2.72(2H, m), 2.79(2H, d, J=6.5Hz),                               3.67(3H, s), 7.25(2H, d, J=8.5Hz),                               7.87(2H, d, J=8.5Hz)     34    Methyl 4-(4-Heptanoyl-                         1738, 0.89(3H, t, J=7.5Hz), 1.28-1.42(6H,           phenyl)butyrate                         1686  m), 1.72(2H, qn, J=7.5Hz), 1.98(2H, qn,           pale yellow oil     J=7.5Hz), 2.34(2H, t, J=7.5Hz), 2.71(2H,                               t, J=7.5Hz), 2.93(2H, t, J=7.5Hz),                               3.67(3H, s), 7.26(2H, d, J=8Hz),                               7.89(2H, d, J=8Hz)     35    Methyl 4-(4-Octanoyl-                         1738, 0.88(3H, t, J=7Hz), 1.24-1.42(8H, m),           phenyl)butyrate                         1684  1.73(2H, qn, J=7.5Hz), 1.98(2H, qn,           colorless needles   J=7.5Hz), 2.34(2H, t, J=7.5Hz), 2.71(2H,           (n-Hexane)          t, J=7.5Hz), 2.93(2H, t, J=7.5Hz),           mp 43˜44.5° C.                               3.67(3H, s), 7.26(2H, d, J=8Hz), 7.88(2H,                               d, J=8Hz)     __________________________________________________________________________

                                      TABLE 11     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     36    Methyl 4-(4-Nonanoyl-                         1744, 0.88(3H, t, J=7Hz), 1.23-1.42(10H, m),           phenyl)butyrate                         1688  1.72(2H, qn, J=7.5Hz), 1.98(2H, qn,           colorless needles   J=7.5Hz), 2.34(2H, t, J=7.5Hz), 2.71(2H,           (n-Hexane)          t, J=7.5Hz), 2.93(2H, t, J=7.5Hz),           mp 35˜35.5° C.                               3.67(3H, s), 7.26(2H, d, J=8Hz), 7.88(2H,                               d, J=8Hz)     37    Methyl 4-[4-(5-Methyl-                         1740, 0.90(6H, d, J=6Hz), 1.24-1.28(2H, m),           hexanoyl)phenyl]butyrate                         1684  1.55-1.64(1H, m), 1.73(2H, qn, J=7.5Hz),           pale brown oil      1.98(2H, qn, J=7.5Hz), 2.34(2H,                               t, J=7.5Hz), 2.71(2H, t, J=7.5Hz), 2.92(2H,                               t, J=7.5Hz), 3.67(3H, s), 7.26(2H,                               d, J=8Hz), 7.88(2H, d, J=8Hz)     38    Methyl 4-[4-(6-Methyl-                         1740, 0.87(6H, d, J=6Hz), 1.18-1.26(2H, m),           heptanoyl)phenyl]butyrate                         1684  1.33-1.41(2H, m), 1.48-1.60(1H, m),           colorless oil       1.71(2H, qn, J=7.5Hz), 1.98(2H, qn,                               J=7.5Hz), 2.34(2H, t, J=7.5Hz), 2.71(2H,                               t, J=7.5Hz), 2.94(2H, t, J=7.5Hz),                               3.67(3H, s), 7.26(2H, d, J=8.5Hz),                               7.89(2H, d, J=8.5Hz)     39    Methyl 4-[4-(4,4-Dimethyl-                         1738, 0.96(9H, s), 1.62-1.65(2H, m), 1.98(2H,           pentanoyl)phenyl]butyrate                         1684  qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),           colorless oil       2.71(2H, t, J=7.5Hz), 2.89-2.93(2H,                               m), 3.67(3H, s), 7.27(2H, d, J=8Hz),                               7.89(2H, d, J=8Hz)     40    Methyl 4-[4-(5,5-Dimethyl-                         1740, 0.90(9H, s), 1.24-1.27(2H, m), 1.67-           hexanoyl)phenyl]butyrate                         1686  1.74(2H, m), 1.98(2H, qn, J=7.5Hz), 2.34(2H,           colorless oil       t, J=7.5Hz), 2.71(2H, t, J=7.5Hz),                               2.91(2H, t, J=7.5Hz), 3.67(3H,                               s), 7.26(2H, d, J=8.5Hz), 7.88(2H, d,                               J=8.5Hz)     41    Methyl 4-[4-(6,6-Dimethyl-                         1742, 0.87(9H, s), 1.20-1.28(2H, m), 1.31-           heptanoyl)phenyl]butyrate                         1686  1.37(2H, m), 1.70(2H, qn, J=7.5Hz), 1.98(2H,           colorless oil       qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),                               2.71(2H, t, J=7.5Hz), 2.95(2H,                               t, J=7.5Hz), 3.67(3H, s), 7.27(2H, d,                               J=8Hz), 7.89(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 12     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     42    Methyl 4-[4-(3-Cyclopentyl-                         1742, 1.10-1.20(2H, m), 1.50-1.55(2H, m),           propionyl)phenyl]butyrate                         1680  1.55-1.65(2H, m), 1.74(2H, q, J=7.5Hz),           pale orange oil     1.70-1.85(3H, m), 1.98(2H, qn, J=7.5Hz),                               2.34(2H, t, J=7.5Hz), 2.71(2H,                               t, J=7.5Hz), 2.95(2H, t, J=7.5Hz),                               3.67(3H, s), 7.26(2H, d, J=8Hz), 7.89(2H,                               d, J=8Hz)     __________________________________________________________________________

Reference Example 43 4-(4-Cinnamoylphenyl)butyric Acid

To a solution of 0.40 g of sodium hydroxide in 6 ml of water, a solution of 1.00 g of methyl 4-(4-acetylphenyl)butyrate in 2 ml of methanol was added under ice-cooling. Then, a solution of 0.48 g of benzaldehyde in 2 ml of methanol was added dropwise and stirring was continued at room temperature for 3 hours. The reaction mixture was diluted with water and acidified with dilute hydrochloric acid. Precipitated crystals were collected by filtration, washed successively with water and n-hexane to yield 0.94 g of colorless crystals. Recrystallization from 80% aqueous methanol gave colorless needles, mp 111°˜112° C.

Analysis for C₁₉ H₁₈ O₃

Calculated C, 77.53; H, 6.16 Found C, 77.54; H, 6.22

The compounds of Reference Examples 44 through 50 shown in Table 13 were obtained in the same manner as described in Reference Example 43.

                                      TABLE 13     __________________________________________________________________________     Reference                      Analysis     Example                        (upper:Calculated)     No.   Compound   Appearance                             mp     (lower:Found     __________________________________________________________________________     44    4-[4-(4-Methyl-                      pale yellow                            148.5˜                                    C.sub.20 H.sub.20 O.sub.3           cinnamoyl)phenyl]-                      plates                            150.5° C.                                    C, 77.90; H, 6.54           butyric Acid                      (MeOH)        C, 77.94; H, 6.48     45    4-[4-(4-Butyl-                      colorless                            108˜109° C.                                    C.sub.23 H.sub.26 O.sub.3           cinnamoyl)phenyl]-                      flakes        C, 78.83; H, 7.48           butyric Acid                      (i-Pr.sub.2 O)                                    C, 78.70; H, 7.60     46    4-[4-(4-Butoxy-                      pale yellow                            105.5˜                                    C.sub.23 H.sub.26 O.sub.4           cinnamoyl)phenyl]-                      needles                            107.5° C.                                    C, 75.38; H, 7.15           butyric Acid                      (MeOH)        C, 75.29; H, 7.22     47    4-[4-(4-Chloro-                      pale yellow                            159˜161° C.                                    C.sub.19 H.sub.17 ClO.sub.3           cinnamoyl)phenyl]-                      needles       C, 69.41; H, 5.21           butyric Acid                      (MeOH)        C, 69.42; H, 4.94     48    4-[4-(4-Fluoro-                      pale yellow                            126˜                                    C.sub.19 H.sub.17 FO.sub.3           cinnamoyl)phenyl]-                      flakes                            129.5° C.                                    C, 73.06; H, 5.49           butyric Acid                      (MeOH)        C, 72.98; H, 5.25     49    4-[4-(3-Fluoro-                      pale yellow                            104˜106° C.                                    C.sub.19 H.sub.17 FO.sub.3           cinnamoyl)phenyl]-                      plates        C, 73.06; H, 5.49           butyric Acid                      (AcOEt-       C, 72.95; H, 5.33                      i-Pr.sub.2 O)     50    4-[4-(1-Oxo-5-phenyl-                      pale yellow                            141˜                                    C.sub.21 H.sub.20 O.sub.3           pentan-2, 4-dien-1-yl)-                      needles                            143.5° C.                                    C, 78.73; H, 6.29           phenyl]butyric Acid                      (AcOEt)       C, 78.54; H, 6.29     __________________________________________________________________________

Reference Example 51 Methyl 4-(4-Cinnamoylphenyl)butyrate

To a solution of 10.00 g of 4-(4-cinnamoylphenyl)butyric acid in 50 ml of methanol, 0.25 ml of sulfuric acid was added, and the mixture was refluxed for 1 hour. The solvent was removed under reduced pressure, and then the residue was added with water and extracted with ether. The ether layer was washed with water and dried, and then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:n-hexane=3:2) to yield 8.94 g of pale yellow crystals. Recrystallization from n-hexane gave pale yellow needles, mp 43°˜44° C.

Analysis for C₂₀ H₂₀ O₃

Calculated C, 77.90; H, 6.54 Found C, 78.10; H, 6.65

The compounds of Reference Examples 52 through 58 shown in Table 14 were obtained in the same manner as described in Reference Example 51.

                                      TABLE 14     __________________________________________________________________________     Reference                       Analysis     Example                         (upper:Calculated)     No.   Compound    Appearance                              mp     (lower:Found     __________________________________________________________________________     52    Methyl 4-[4-(4-Methyl-                       pale yellow                              102.5˜                                     C.sub.21 H.sub.22 O.sub.3           cinnamoyl)phenyl]-                       flakes 104° C.                                     C, 78.23; H, 6.88           butyrate    (AcOEt)       C, 78.27; H, 7.00     53    Methyl 4-[4-(4-Butyl-                       pale yellow                              57˜58° C.                                     C.sub.24 H.sub.28 O.sub.3           cinnamoyl)phenyl]-                       needles       C, 79.09; H, 7.74           butyrate    (i-Pr.sub.2 O-                                     C, 79.17; H, 8.03                       n-Hexane)     54    Methyl 4-[4-(4-Butoxy-                       pale yellow                              70˜71.5° C.                                     C.sub.24 H.sub.28 O.sub.4           cinnamoyl)phenyl]-                       needles       C, 75.76; H, 7.42           butyrate    (i-Pr.sub.2 O)                                     C, 75.82; H, 7.63     55    Methyl 4-[4-(4-Chloro-                       pale yellow                              116˜118° C.                                     C.sub.20 H.sub.19 ClO.sub.3           cinnamoyl)phenyl]-                       flakes        C, 70.07; H, 5.59           butyrate    (AcOEt)       C, 70.04; H, 5.57     56    Methyl 4-[4-(4-Fluoro-                       pale yellow                              100.5˜                                     C.sub.20 H.sub.19 FO.sub.3           cinnamoyl)phenyl]-                       plates 101.5° C.                                     C, 73.60; H, 5.87           butyrate    (MeOH)        C, 73.74; H, 5.91     57    Methyl 4-[4-(3-Fluoro-                       pale yellow                              54˜54.5° C.                                     C.sub.20 H.sub.19 FO.sub.3           cinnamoyl)phenyl]-                       plates        C, 73.60; H, 5.87           butyrate    (i-Pr.sub.2 O)                                     C, 73.65; H, 5.89     58    Methyl 4-[4-(1-Oxo-5-                       pale yellow                              81˜82.5° C.                                     C.sub.22 H.sub.22 O.sub.3           phenylpentan-2,4-dien-                       flakes        C, 79.02; H, 6.63           1-yl)phenyl]butyrate                       (MeOH)        C, 79.02; H, 6.75     __________________________________________________________________________

Reference Example 59 Methyl 4-[4-(3-Phenylpropionyl)phenyl]butyrate

To a solution of 3.89 g of methyl 4-(4-cinnamoylphenyl)butyrate in 50 ml of methanol, 0.25 g of 10% palladium on carbon was added, and hydrogenation was carried out at an ordinary temperature and under ordinary pressure for 5 hours. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to give 3.87 g of pale brown oil.

IR spectrum ν (liq) cm⁻¹ : 1738, 1684

Mass spectrum m/z: 310 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.97(2H,qn,J=7.5 Hz), 2.33(2H,t,J=7.5 Hz), 2.70(2H,t,J=7.5 Hz), 3.06(2H,t,J=8 Hz), 3.28(2H,t,J=8 Hz), 3.67(3H,s), 7.15-7.32(7H,m), 7.89(2H,d,J=8 Hz)

The compounds of Reference Examples 60 and 61 shown in Tables 15 and 16 were obtained in the same manner as described in Reference Example 59.

                                      TABLE 15     __________________________________________________________________________     Reference                    Analysis     Example                      (upper:Calculated)     No.   Compound  Appearance                            mp    (lower:Found     __________________________________________________________________________     60    Methyl 4-[4-[3-(4-                     pale yellow                            59˜60° C.                                  C.sub.24 H.sub.30 O.sub.4           Butoxyphenyl)-                     needles      C, 75.36; H, 7.91           propionyl]phenyl]-                     (MeOH)       C, 75.23; H, 8.13           butyrate     __________________________________________________________________________

                                      TABLE 16     __________________________________________________________________________     Reference     Example           Compound    I R ν                             NMR     No.   Appearance  (liq) cm.sup.-1                             δ (CDCl.sub.3)     __________________________________________________________________________     61    Methyl 4-[4-(5-Phenyl-                       1738, 1.68-1.83(4H, m), 1.97(2H, qn, J=7.5Hz),           valeryl)phenyl]butyrate                       1684  2.34(2H, t, J=7.5Hz), 2.67(2H, t,           colorless oil     J=7.5Hz), 2.71(2H, t, J=7.5Hz), 2.96(2H,                             t, J=7.5Hz), 3.67(3H, s), 7.14-                             7.30(7H, m), 7.87(2H, d, J=8.5Hz)     __________________________________________________________________________

Reference Example 62 Methyl 4-(4-Ethoxycarbonylacetylphenyl)butyrate

To a solution of 20.0 g of methyl 4-phenylbutyrate in 100 ml of carbon disulfide, 44.9 g of anhydrous aluminium chloride was added under ice-cooling, and then 16.9 g of ethyl malonyl chloride was added dropwise. After being heated under reflux for 1.5 hours, the reaction mixture was poured into ice-water and then extracted with ether. After the ether layer was washed successively with water, aqueous potassium carbonate solution and water and then dried, the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride) to yield 20.2 g of a pale yellow oil.

IR spectrum ν (liq) cm⁻¹ : 1738, 1688

Mass spectrum m/z: 292 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.26(3H,t,J=7.5 Hz), 1.98(2H,qn,J=7.5 Hz), 2.34(2H,t,J=7.5 Hz), 2.72(2H,t,J=7.5 Hz), 3.67(3H,s), 3.96(2H,s), 4.21(2H,q,J=7.5 Hz), 7.29(2H,d,J=8.5 Hz), 7.87(2H,d,J=8.5 Hz)

Reference Example 63 Methyl 4-[4-[α-Ethoxycarbonyl-α-(2-phenylethyl)]acetylphenyl]butyrate

0.92 g of 60% sodium hydride was added to 10 ml of dry N,N-dimethylformamide under ice-cooling, and then a solution of 6.70 g of methyl 4-(4-ethoxycarbonylacetylphenyl)butylate in 16 ml of dry N,N-dimethylformamide was added dropwise and stirring was contiuned at room temperature for 10 minutes. To the reaction mixture, a solution of 4.24 g of β-bromoethylbenzene in 13 ml of N,N-dimethylformamide was added dropwise at room temperature, and then stirring was continued at 100° C. under heating for 1 hour. After being cooled, the reaction mixture was poured into dilute hydrochloric acid and then extracted with ether. The ether layer was washed with water and dried, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:n-hexane=3:1→5:1) to yield 3.88 g of colorless oil.

IR spectrum ν (liq) cm⁻¹ : 1738, 1686

Mass spectrum m/z: 396 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.18(3H,t,J=7.5 Hz), 1.97(2H,qn,J=7.5 Hz), 2.26-2.39(2H,m), 2.34(2H,t,J=7.5 Hz), 2.63-2.74(2H,m), 2.70(2H,t,J=7.5 Hz), 3.67(3H,s), 4.16(2H,q,J=7.5 Hz), 4.26(1H,t,J=7.5 Hz), 7.15-7.31(1H,m), 7.81(2H,d,J=8.5 Hz)

The compound of Reference Example 64 was obtained in the same manner as described in Reference Example 63.

Reference Example 64 Ethyl 6-Phenyl-2-[4-(3-methoxycarbonylpropyl)benzoyl]hexanoate

Appearance colorless viscous oil

IR spectrum ν (liq) cm⁻¹ : 1738, 1686

Mass spectrum m/z: 424 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.16(3H,t,J=7.5 Hz), 1.40(2H,qn,J=7.5 Hz), 1.62-1.70(2H,m), 1.94-2.07(4H,m), 2.34(2H,t,J=7.5 Hz), 2.60(2H,t,J=7.5 Hz), 2.72(2H,t,J=7.5 Hz), 3.67(3H,s), 4.13(2H,qd,J=7.5,2 Hz), 4.24(2H,t,J=7 Hz), 7.13-7.19(4H,m), 7.24-7.29(3H,m), 7.90(2H,d,J=8 Hz)

Reference Example 65 4-[4-(4-Phenylbutyryl)phenyl]butyric Acid

A mixture of 1.90 g of methyl 4-[4-(α-ethoxycarbonyl-α-(2-phenylethyl)]acetylphenyl butyrate, 29 ml of sulfuric acid, 9.5 ml of acetic acid and 5.7 ml of water was refluxed for 17 hours. After being cooled, the reaction mixture was added with water and extracted with methylene chloride. The methylene chloride layer was washed with water and dried, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:ethyl acetate=2:1) to yield 0.82 g of colorless crystals. Recrystallization from ethyl acetate gave colorless flakes, mp 111°˜111.5° C.

Analysis for C₂₀ H₂₂ O₃

Calculated C, 77.39; H, 7.14 Found C, 77.53 ; H, 7.31

The compound of Reference Example 66 was obtained in the same manner as described in Reference Example 65.

Reference Example 66 4-[4-(6-Phenylhexanoyl)phenyl]butyric Acid

Appearance colorless needles (AcOEt)

mp 86°˜89° C.

Analysis for C₂₂ H₂₆ O₃

Calculated C, 78.07; H, 7.74 Found C, 78.07; H, 7.99

Reference Example 67 Methyl 4-[4-(4-phenylbutyryl)phenyl]butyrate

To a suspension of 2.10 g of 4-[4-(4-phenylbutyryl)phenyl]butyric acid in 15 ml of methanol, 0.1 ml of sulfuric acid was added, and the mixture was heated under reflux for 4 hours. After the reaction solution was removed under reduced pressure, the residue was dissolved in ethyl acetate and then washed successively with water, aqueous potassium carbonate and water. After the ethyl acetate layer was dried, the solvent was removed under reduced pressure. The residue was washed with isopropyl ether to yield 1.87 g of colorless crystals. Recrystallization from methanol gave colorless flakes, mp 61°˜62° C.

Analysis for C₂₁ H₂₄ O₃

Calculated C, 77.75; H, 7.46 Found C, 77.62; H, 7.32

The compound of Reference Example 68 was obtained in the same manner as described in Reference Example 67.

Reference Example 68 Methyl 4-[4-(6-Phenylhexanoyl)phenyl]butyrate

Appearance colorless flakes (MeOH)

mp 45.5°˜46.5° C.

Analysis for C₂₃ H₂₈ O₃

Calculated C, 78.38; H, 8.01 Found C, 78.24; H, 7.92

Reference Example 69 Methyl 4-[4-(1-Hydroxy-2-phenylethyl)phenyl]butyrate

To a suspension of 20.0 g of methyl 4-[4-(phenylacetyl)phenyl]butyrate in 200 ml of methanol, 2.52 g of sodium borohydride was added portionwise under ice-cooling, and stirring was continued for 1 hour. After the reaction solvent was removed under reduced pressure, the residue was added with water and then extracted with ether. After the ether layer was washed with water and dried, the solvent was removed to yield 20.3 g of pale yellow oil.

IR spectrum ν (liq) cm⁻¹ : 3464, 1738

Mass spectrum m/z: 298 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.95(2H,qn,J=7.5 Hz), 2.33(2H,t,J=7.5 Hz), 2.65(2H,t,J=7.5 Hz), 2.98(1H,dd,J=14,8.5 Hz), 3.03(1H,dd,J=14,5 Hz), 3.67(3H,s), 4.87(1H,dd,J=8.5,5 Hz), 7.15-7.30(9H,m)

The compounds of Reference Examples 70 through 115 shown in Tables 17 to 26 were obtained in the same manner as described in Reference Example 69.

                                      TABLE 17     __________________________________________________________________________     Reference                       Analysis     Example                         (upper: Calculated)     No.   Compound    Appearance                              mp     (lower: Found)     __________________________________________________________________________     70    Methyl 3-[4-(1-Hydroxy-                       colorless                              38˜39.5° C.                                     C.sub.18 H.sub.20 O.sub.3           2-phenylethyl)phenyl]-                       flakes        C, 76.03; H, 7.09           propionate  (i-Pr.sub.2 O)                                     C, 76.05; H, 7.38     71    Methyl 4-[4-[2-(4-                       colorless                              45˜46.5° C.                                     C.sub.19 H.sub.21 ClO.sub.3           Chlorophenyl)-1-                       needles       C, 68.57; H, 6.36           hydroxyethyl]phenyl]-                       (i-Pr.sub.2 O-                                     C, 68.73; H, 6.63           butyrate    n-Hexane)     72    Methyl 5-[4-(1-Hydroxy-                       colorless                              46.5˜47.5° C.                                     C.sub.20 H.sub.24 O.sub.3           2-phenylethyl)phenyl]-                       columns       C, 76.89; H, 7.74           valerate    (i-Pr.sub.2 O)                                     C, 77.04; H, 8.01     __________________________________________________________________________

                                      TABLE 18     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     73    Methyl 4-(4-[2-(2-Fluoro-                        3464, 1.91(1H, d, J=3Hz), 1.95(2H, qn, J=7.5Hz,           phenyl)-1-hydroxyethyl]-                        1738  2.32(2H, t, J=7.5Hz), 2.65(2H,           phenyl]butyrate    t, J=7.5Hz), 3.01(1H, dd, J=13.5, 8.5Hz),           pale brown oil     3.09(1H, dd, J=13.5, 5Hz), 3.67                              (3H, s), 4.93(1H, m), 7.01-7.08(2H, m),                              7.15(2H, d, J=8.5Hz), 7.16-7.24(2H,                              m), 7.29(2H, d, J=8.5Hz)     74    Methyl 4-[4-[2-(3-Fluoro-                        3464, 1.90(1H, d, J=3Hz), 1.95(2H, qn, J=7.5Hz),           phenyl)-1-hydroxyethyl]-                        1738  2.33(2H, t, J=7.5Hz), 2.65(2H,           phenyl]butyrate    t, J=7.5Hz), 3.00(2H, d, J=6.5Hz), 3.67           pale brown oil     (3H, s), 4.87(1H, td, J=6.5, 3Hz), 6.88-                              6.95(2H, m), 6.96(1H, d, J=7.5Hz),                              7.16(2H, d, J=8Hz), 7.22-7.28(1H,                              m), 7.26(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 19     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     75    Methyl 4-[4-[2-(4-Fluoro-                        3464, 1.79(1H, brs), 1.95(2H, qn, J=7.5Hz),           phenyl)-1-hydroxyethyl]-                        1738  2.32(2H, t, J=7.5Hz), 2.65(2H, t, J=           phenyl]butyrate    7.5Hz), 2.98(2H, d, J=6.5Hz), 3.67(3H,           pale brown oil     s), 4.83(1H, t, J=6.5Hz), 6.96(2H,                              t, J=8.5Hz), 7.12(2H, dd, J=8.5, 5.5Hz),                              7.15(2H, d, J=8Hz), 7.24(2H, d, J=8Hz)     76    Methyl 4-[4-[1-Hydroxy-2-                        3464, 1.95(2H, qn, J=7.5Hz), 2.32(3H, s), 2.33           (p-tolyl)ethyl]phenyl]-                        1738  (2H, t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),           butyrate           2.92(1H, dd, J=14, 8.5Hz), 3.00           pale yellow oil    (1H, dd, J=14, 5Hz), 3.67(3H, s), 4.84                              (1H, dd, J=8.5, 5Hz), 7.09(2H, d, J=8.5Hz),                              7.11(2H, d, J=8.5Hz), 7.16(2H,                              d, J=8Hz), 7.24(2H, d, J=8Hz)     77    Methyl 4-[4-(1-Hydroxy-                        3432, 1.49(3H, d, J=6.5Hz), 1.69(1H, brs),           ethyl)phenyl]butyrate                        1738  1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           pale yellow oil    7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.88(1H, q, J=6.5Hz), 7.16(2H,                              d, J=8.5Hz), 7.30(2H, d, J=8.5Hz)     78    Methyl 4-[4-(1-Hydroxy-                        3460, 0.92(3H, t, J=7.5Hz), 1.67-1.85(3H,           propyl)phenyl]butyrate                        1738  m), 1.95(2H, qn, J=7.5Hz), 2.33(2H, t,           pale yellow oil    J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66                              (3H, s), 4.57(1H, t, J=7Hz), 7.16(2H,                              d, J=8Hz), 7.26(2H, d, J=8Hz)     79    Methyl 4-(4-(1-Hydroxy-                        3432, 0.93(3H, t, J=7.5Hz), 1.26-1.36(1H,           butyl)phenyl]butyrate                        1738  m), 1.38-1.48(1H, m), I.63-1.71(1H,           colorless oil      m), 1.74-1.83(2H, m), 1.95(2H, qn, J=                              7.5Hz), 2.33(2H, t, J=7.5Hz), 2.64(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.63-4.67                              (1H, m), 7.15(2H, d, J=8.5Hz), 7.26                              (2H, d, J=8.5Hz)     80    Methyl 4-[4-(1-Hydroxy-                        3432, 0.89(3H, t, J=7Hz), 1.20-1.45(2H, m),           pentyl)phenyl]butyrate                        1738  1.34(2H, qn, J=7Hz), 1.65-1.75(1H,           colorless oil      m), 1.76-1.85(1H, m), 1.77(1H, d, J=3Hz),                              1.95(2H, qn, J=7.5Hz), 2.33(2H,                              t, J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                              (3H, s), 4.61-4.66(1H, m), 7.16(2H,                              d, J=8Hz), 7.26(2H, d, J-8Hz)     __________________________________________________________________________

    __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     81    Methyl 4-[4-(1-Hydroxy-                         3432, 0.87(3H, t, J=7Hz), 1.20-1.37(5H, m),           hexyl)phenyl]butyrate                         1738  1.36-1.45(1H, m), 1.66-1.74(1H, m),           colorless oil       1.75-1.84(IH, m), 1.75(1H, d, J=3.5Hz),                               1.95(2H, qn, J=7.5Hz), 2.33(2H,                               t, J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                               (3H, s), 4.60-4.67(1H, m), 7.16(2H,                               d, J=8Hz), 7.26(2H, d, J=8Hz)     82    Methyl 4-[4-(1-Hydroxy-                         3424, 0.87(3H, t, J=7Hz), 1.20-1.36(13H, m),           decyl)phenyl]butyrate                         1742  1.38-1.42(1H, m), 1.66-1.72(1H, m),           pale yellow oil     ), 1.75(1H, d, J=4Hz), 1.76-1.82(1H,                               m), 1.95(2H, qn, J=7.5Hz), 2.33(2H, t,                               J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                               (3H, s), 4.61-4.65(1H, m), 7.15(2H,                               d, J=8Hz), 7.26(2H, d, J=8Hz)     83    Methyl 4-[4-(1-Hydroxy-3-                         3432, 0.94(3H, d, J=6.5Hz), 0.95(3H, d, J=6.5Hz),           methylbutyl)phenyl]-                         1738  1.47-1.53(1H, m), 1.66-1.76           butyrate            (2H, m), 1.71(1H, d, J=3Hz), 1.95(2H, qn,           colorless oil       J=7.5Hz), 2.33(2H, t, J=7.5Hz), 2.64                               (2H, t, J=7.5Hz), 3.67(3H, s), 4.70-                               4.73(1H, m), 7.16(2H, d, J=8Hz), 7.27                               (2H, d, J=8Hz)     84    Methyl 4-[4-(1-Hydroxy-4-                         3432, 0.87(3H, d, J=6.5Hz), O.88(3H, d, J=6.5Hz),           methylpentyl)phenyl]-                         1738  1.10-1.17(IH, m), 1.29-1.36           butyrate            (1H, m), 1.50-1.60(1H, m), 1.66-1.74           colorless oil       (1H, m), 1.76(1H, d, J=3Hz), 1.77-1.83                               (1H, m), 1.95(2H, qn, J=7.5Hz), 2.33                               (2H, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                               3.67(3H, s), 4.59-4.62(1H, m), 7.16                               (2H, d, J=8Hz), 7.26(2H, d, J=8Hz)     85    Methyl 4-[4-(3, 3-Dimethyl-                         3464, 0.99(9H, s), 1.56(1H, s), 1.62(1H, dd,           1-hydroxybutyl)phenyl]-                         1738  J=14, 4Hz), 1.75(IH, dd, J=14, 8.5Hz),           butyrate            1.95(2H, qn, J=7.5Hz), 2.32(2H, t,           colorless oil       J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                               (3H, s), 4.80(1H, dt, J=8.5, 4Hz), 7.15                               (2H, d, J=8Hz), 7.26(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 21     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     86    Methyl 4-[4-(Cyclopentyl-                         3464, 1.12-1.16(1H, m), 1.36-1.66(6H, m),           hydroxymethyl)phenyl]-                         1738  1.87-1.91(1H, m), 1.70(1H, s), 1.95           butyrate            (2H, qn, J=7.5Hz), 2.21(2H, sex, J=8.5Hz),           pale yellow oil     2.33(2H, t, J=7.5Hz), 2.64(2H, t,                               J=7.5Hz), 3.67(3H, s), 4.37(1H, d, J=                               8.5Hz), 7.14(2H, d, J=8Hz), 7.26(2H,                               d, J=8Hz)     87    Methyl 4-[4-(Cyclohexyl-                         3516, 0.86-0.96(1H, m), O.99-1.30(4H, m),           hydroxymethyl)phenyl]-                         1738  1.33-1.40(1H, m), 1.54-1.80(5H, m),           butyrate            1.90-2.02(1H, m), 1.95(2H, qn, J=7.5Hz),           colorless oil       2.33(2H, t, J=7.5Hz), 2.64(2H, t,                               J=7.5Hz), 3.67(3H, s), 4.33(1H, d, J=                               7.5Hz), 7.14(2H, d, J=8Hz), 7.21(2H,                               d, J=8Hz)     88    Methyl 4-[4-(Cycloheptyl-                         3464, 1.10-1.19(1H, m), 1.29-1.93(13H, m),           hydroxymethyl)phenyl]-                         1740  1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           butyrate            7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66           pale brown oil      (3H, s), 4.43(1H, d, J=6.5Hz), 7.14(2H,                               d, J=8Hz), 7.23(2H, d, J=8Hz)     89    Methyl 4-[4-(2-Cyclopentyl-                         3440, 1.08-1.20(2H, m), 1.46-1.54(2H, m),           1-hydroxyethyl)phenyl]-                         1742  1.56-1.64(2H, m), 1.66-1.72(1H, m),           butyrate            1.74(1H, s), 1.77-1.88(4H, m), 1.95           colorless oil       (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               )2.64(2H, t, J=7.5Hz), 3.66(3H, s),                               4.67(1H, t, J=7Hz), 7.15(2H, d, J=8Hz),                               7.27(2H, d, J=8Hz)     90    Methyl 4-[4-(2-Cyclohexyl-                         3448, 0.88-1.02(2H, m), 1.11-1.29(3H, m),           1-hydroxyethyl)phenyl]-                         1742  1.37-1.46(1H, m), 1.48-1.54(1H, m),           butyrate            1.62-1.84(6H, m), 1.68(1H, s), 1.95           colorless oil       (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.64(2H, t, J=7.5Hz), 3.66(3H, s),                               4.76(1H, dd, J=9, 5Hz), 7.15(2H, d, J=                               8Hz), 7.26(2H, d, J=8Hz)     91    Methyl 4-[4-(3-Cyclohexyl-                         3460, 0.80-0.90(2H, m), 1.08-1.27(5H, m),           1-hydroxypropyl)phenyl]-                         1740  1.27-1.37(1H, m), 1.58-1.84(7H, m),           butyrate            1.79(1H, d, J=3.5Hz), 1.95(2H, qn, J=           pale brown oil      7.5Hz), 2.33(2H, t, J=7.5Hz), 2.64(2H,                               t, J=7.5-Hz), 3.66(3H, s), 4.57-4.63                               (1H, m), 7.15(2H, d, J=8Hz), 7.25(2H,                               d, J=8Hz)     __________________________________________________________________________

                                      TABLE 22     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               (CDCl.sub.3)     __________________________________________________________________________     92    Methyl 4-[4-(4-Cyclohexyl-                         3432, 0.80-0.90(2H, m), 1.08-1.33(7H, m),           1-hydroxybutyl)phenyl]-                         1740  1.38-1.48(1H, m), 1.60-1.70(6H, m),           butyrate            1.73-1.81(1H, m), 1.77(1H, s), 1.95           pale yellow oil     (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.64(2H, t, J=7.5Hz), 3.67(3H, s),                               4.63(1H, t, J=6Hz), 7.15(2H, d, J=8Hz),                               7.26(2H, d, J=8Hz)                               87(2H, m), 1.08-1.43(10H, m)     93    Methyl 4-[4-(5-Cyclohexyl-                         3444, 0.80-0.87(2H, m), 1.08-1.43(10H,m),           1-hydroxypentyl)phenyl]-                         1742  1.60-1.72(6H, m), 1.75-1.82(1H, m),           butyrate            1.82(1H, s), 1.95(2H, qn, J=7.5Hz),           pale yellow oil     2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                               3.66(3H, s), 4.62(1H, m), 7.15                               (2H, d, J=8Hz), 7.25(2H, d, J=8Hz)     94    Methyl 4-[4-(6-Cyclohexyl-                         3460, 0.78-0.90(2H, m), 1.08-1.46(12H, m),           1-hydroxyhexyl)phenyl]-                         1738  1.60-1.85(7H, m), 1.76(1H, d, J=3Hz),           butyrate            1.95(2H, qn, J=7.5Hz), 2.33(2H, t,           colorless oil       J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66                               (3H, s), 4.60-4.65(1H, m), 7.16(2H, d,                               J=8Hz), 7.26(2H, d, J=8Hz)     95    Methyl trans-4-[4-                         3464, 0.78-1.12(4H, m), O.85(3H, d, J=6Hz),           (Hydroxy(4-methylcyclo-                         1738  1.21-1.39(2H, m), I.50-1.66(2H, m),           hexyl)methyl]phenyl]-                               1.70-1.76(1H, m), 1.78(1H, d, J=3Hz),           butyrate            1.95(2H, qn, J=7.5Hz), 1.98-2.04           colorless oil       (1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                               t, J=7.5Hz), 3.67(3H, s), 4.32(IH, dd,                               J=7.5, 3Hz), 7.14(2H, d, J=8.5Hz),                               7.21(2H, d, J=8.5Hz)     96    Methyl trans-4-[4-                         (KBr) 0.78-1.32(13H, m), O.87(3H, t, J=7Hz),           [Hydroxy(4-pentylcyclo-                         3436, I.36-1.40(1H, m), I.52-1.60(1H, m),           hexyl)methyl]phenyl]-                         1738  1.65-1.71(1H, m), 1.76-1.82(2H, m),           butyrate            1.95(2H, qn, J=7.5Hz), 1.98-2.05           colorless amorphous solid                               (1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                               t, J=7.5Hz), 3.67(3H, s), 4.32(1H, dd,                               J=7, 2.5Hz), 7.14(2H, d, J=8Hz), 7.21                               21(2H, d, J=8Hz)     97    Methyl 4-[4-[2-(l-                         3448, 1.58-1.72(14H, m), 1.92-1.98(5H, m),           Adamantyl)-1-hydroxyethyl]                         1740  2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=           phenyl]butyrate     7.5Hz), 3.67(3H, s), 4.87(1H, in), 7.14           colorless oil       4(2H, d, J=8Hz), 7.25(2H, d, J=8Hz)     __________________________________________________________________________

    __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               (CDCl.sub.3)     __________________________________________________________________________      98   Methyl 4-[4-1-Hydroxy-2-                         3432, 1.05-1.16(4H, m), 1.30-1.32(1H, m),           (2-norbornyl)ethyl]phenyl]-                         1738  1.40-1.52(4H, m), 1.62-1.70(3H, m),           butyrate            1.92-1.98(3H, m), 2.19(1H, s), 2.32           pale yellow oil     (2H, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                               3.69(3H, s), 4.64(1H, m), 7.16(2H, d,                               J=8Hz), 7.25(2H, d, J=8Hz)      99   Methyl 4-[4-(1-Hydroxy-3-                         3436, 1.71(1H, brs), 1.95(2H, qn, J=7.5Hz),           phenylpropyl)phenyl]-                         1738  1.98-2.06(1H, m), 2.09-2.17(1H, m),           butyrate            2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=           colorless oil       7.5Hz), 2.64-2.70(1H, m), 2.75(1H, ddd,                               J=14, 9.5, 6Hz), 3.66(3H, s), 4.66                               (1H, dd, J=8.5, 5Hz), 7.17-7.21(5H, m),                               7.25-7.30(4H, m)     100   Methyl 5-[4-(1-Hydroxy-                         3464, 0.89(3H, t, J=7Hz), 1.19-1.45(4H, m),           pentyl)phenyl]valerate                         1740  1.54-1.84(6H, m), 1.76(1H, d, J=3.5Hz),           colorless oil       2.33(2H, t, J=7Hz), 2.62(2H, t, J=                               7.5Hz), 3.66(3H, s), 4.60-4.66(1H,                               m), 7.15(2H, d, J=8.5Hz), 7.25(2H, d,                               J=8.5Hz)     101   Methyl 5-[4-(1-Hydroxy-                         3464, 0.84-0.89(3H, m), 1.20-1.37(5H, m),           hexyl)phenyl]valerate                         1740  1.37-1.48(1H, m), 1.60-1.83(6H, m),           colorless oil       1.76(1H, d, J=3.5Hz), 2.33(2H, t, J=7Hz),                               2.62(2H, t, J=7Hz), 3.66(3H, s),                               4.60-4.66(1H, m), 7.15(2H, d, J=8.5Hz),                               7.25(2H, d, J=8.5Hz)     102   Methyl 5-[4-(2-Cyclohexyl-                         3456, 0.88-1.02(2H, m), 1.10-1.29(3H, m),           1-hydroxyethyl)phenyl]-                         1738  1.36-1.46(1H, m), 1.47-1.54(1H, m),           valerate            1.58-1.84(10H, m), 1.72(1H, d, J=3Hz),           pale brown oil      2.33(2H, t, J=7Hz), 2.62(2H, t, J=7.5Hz),                               3.66(3H, s), 4.75-4.79(1H, brs),                               7.14(2H, d, J=8Hz), 7.25(2H, d, J=8Hz)     103   Methyl 4-[4-(1-Hydroxy-                         3444, 0.87(3H, t, J=7.5Hz), I.19-1.34(7H,           heptyl)phenyl]butyrate                         1740  m), 1.37-1.45(1H, m), 1.60-1.72(1H,           colorless oil       m), 1.75-1.83(1H, m), 1.77(1H, d, J=3.5Hz),                               1.95(2H, qn, J=7.5Hz), 2.33(2H,                               t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                               3.67(3H, s), 4.63(1H, t, J=6.5Hz)7.15                               5(2H, d, J=8Hz), 7.26(2H, d, J=8Hz)     __________________________________________________________________________

    __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     104   Methyl 4-[4-(1-Hydroxy-                        3542. 0.87(3H, t, J=7Hz), 1.19-1.32(9H, m),           octyl)phenyl]butyrate                        1742  1.36-1.44(1H, m), 1.64-1.72(1H, m),           colorless oil      1.75-1.82(1H, m), 1.78(1H, d, J=3Hz),                              1.95(2H, t, J=7.5Hz), 2.33(2H, t, J=                              7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                              (3H, s), 4.63(1H, t, J=6Hz)7.16(2H, d,                              J=8Hz), 7.26(2H, d, J=8Hz)     105   4-[4-(1-Hydroxy-                        3440, 0.87(3H, t, J=7Hz), 1.19-1.33(11H, m,           phenyl]butyrate                        1742  ), 1.36-1.44(1H, m), 1.65-1.72(1H, m           pale brown oil     ), 1.75-1.82(1H, m), 1.78(1H, s), 1.9                              5(2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5                              Hz), 2.64(2H, t, J=7.5Hz), 3.66(3H, s                              ), 4.63(1H, t, J=6.5Hz)7.15(2H, d, J=                              8Hz), 7.26(2H, d, J=8Hz)     106   Methyl 4-[4-(1-Hydroxy-5-                        3448, 0.85(3H, d, J=7Hz), 0.85(3H, d, J=7Hz           methylhexyl)phenyl]-                        1740  ), 1.17-1.21(2H, m), 1.21-1.32(1H, m           butyrate           ), 1.38-1.47(1H, m), 1.48-1.58(1H, m           pale yellow oil    ), 1.63-1.71(1H, m), 1.74-1.82(1H, m                              ), 1.76(1H, d, J=3Hz), 1.95(2H, qn, J=                              7.5Hz), 2.33(2H, t, J=7.5Hz), 2.64(2                              H, t, J=7.5Hz), 3.67(3H, s), 4.64(1H,                              t, J=6.5Hz), 7.16(2H, d, J=8Hz), 7.26                              (2H, d, J=8Hz)     107   Methyl 4-[4-(1-Hydroxy-6-                        3448, 0.85(6H, d, J=6.5Hz), 1.12-1.19(2H,           methylheptyl)phenyl]-                        1738  m), 1.19-1.44(4H, m), 1.44-1.55(1H,           butyrate           m), 1.65-1.74(1H, m), 1.76(1H, d, J=3           colorless oil      .5Hz), 1.75-1.84(1H, m), 1.95(2H, qn                              J=7.5Hz), 2.33(2H, t, J=7.5Hz), 2.6                              4(2H, t, J=7.5Hz), 3.67(3H, s), 4.61-                              4.66(1H, m), 7.16(2H, d, J=8Hz), 7.26                              (2H, d, J=8Hz)     108   Methyl 4-[4-(4,4-Dimethyl-                        3456, 0.86(9H, s), 1.09(1H, td, J=13, 4.5Hz           1-hydroxypentyl)phenyl]-                        1738  ), 1.37(1H, td, J=13, 4.5Hz), 1.63-1.           butyrate           81(2H, m), I.80(IH, brs), 1.95(2H, qn           colorless oil      , J=7.5Hz), 2.33(2H, t, J=7.5Hz), 2.6                              4(2H, t, J=7.5Hz), 3.67(3H, s), 4.57                              1H, t, J=7Hz), 7.16(2H, d, J=8Hz), 7.2                              6(2H, d, J=8Hz)     __________________________________________________________________________

    __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq (cm.sup.-1)                               δ (CDCl.sub.3)     __________________________________________________________________________     109   Methyl 4-[4-(5,5-Dimethyl-                         3452, 0.85(9H, s), 1.17-1.31(3H, m), 1.36-           1-hydroxyhexyl)phenyl]                         1740  1.46(1H, m), 1.59-1.69(1H, m), 1.72-           butyrate            1.82(1H, m), 1.77(1H, d, J=3.5Hz), l.95           colorless oil       (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.64(2H, t, J=7.5Hz), 3.66(3H,                               s), 4.63-4.67(1H, m), 7.16(2H, d, J=8Hz),                               7.26(2H, d, J=8Hz)     110   Methyl 4-[4-(6,6-Dimethyl-                         3464, 0.84(9H, s), 1.12-1.17(2H, m), 1.20-           1-hydroxyheptyl)phenyl]-                         1742  1.30(3H, m), 1.34-1.43(1H, m), 1.65-           butyrate            1.74(1H, m), 1.76-1.84(1H, m), 1.72           colorless oil       (1H, brs), 1.95(2H, qn, J=7.5Hz), 2.33                               (2H, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                               3.67(3H, s), 4.63(1H, t, J=5.5Hz)7.16                               (2H, d, J=8Hz), 7.26(2H, d, J=8Hz)     111   Methyl 4-8 4-(3-Cyclopentyl-                         3448, 1.00-1.10(2H, m), 1.20-1.30(1H, m),           1-hydroxyphenyl)phenyl]-                         1740  1.40-1.60(5H, m), 1.65-1.85(6H, m),           butyrate            1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           pale yellow oil     7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.60-4.65(1H, m), 7.16(2H, d, J=                               8Hz), 7.26(2H, d, J=8Hz)     112   Methyl 4-[4-[3-(4-Butoxy                         3464, 0.97(3H, t, J=7.5Hz), I.48(2H, sex, J=           phenyl)-1-hydroxypropyl]-                         1738  7.5Hz), 1.72-1.78(2H, m), 1.80(1H,           phenyl]butyrate     d, J=3.5Hz), 1.95(2H, qn, J=7.5Hz), l.19-           pale yellow oil     2.02(1H, m), 2.04-2.13(1H, m), 2.33                               (2H, t, J=7.5Hz), 2.56-2.71(2H, m),                               2.64(2H, t, J=7.5Hz), 3.66(3H, s),                               3.93(2H, t, J=7Hz), 4.62-4.66(1H, m),                               6.81(2H, d, J=8.5Hz), 7.09(2H, d, J=                               8.5Hz), 7.16(2H, d, J=8Hz), 7.25(2H,                               d, J=8Hz)     113   Methyl 4-[4-(1-Hydroxy-4-                         3460, 1.58-1.66(1H, m), 1.68-1.88(4H, m),           phenylbutyl)phenyl]-                         1738  1.94(2H, qn, J=7.5Hz), 2.32(2H, t, J=           butyrate            7.5Hz), 2.60-2.65(4H, m), 3.66(3H, s),           colorless oil       4.63-4.67(1H, m), 7.12-7.18(5H, m),                               7.22-7.27(4H, m)     __________________________________________________________________________

    __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     114   Methyl 4-[4-(1-Hydroxy-5-                        3448, 1.28-1.38(1H, m), 1.43-1.53(1H, m),           phenylpentyl)phenyl]-                        1738  1.60-1.87(5H, m), 1.95(2H, qn, J=7.5Hz),           butyrate           2.33(2H, t, J=7.5Hz), 2.59(2H, t,           colorless oil      J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66                              (3H, s), 4.59-4.65(1H, m), 7.12-7.18                              (5H, m), 7.22-7.28(4H, m)     115   Methyl 4-[4-(1-Hydroxy-6-                        3432, 1.18-1.50(4H, m), 1.55-1.83(5H, m),           phenylhexyl)phenyl]-                        1738  1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           butyrate           7.5Hz), 2.58(2H, t, J=7.5Hz), 2.64(2H,           colorless oil      t, J=7.5Hz), 3.66(3H, s), 4.58-4.69                              (1H, m), 7.12-7.19(5H, m), 7.22-7.28(4H,     __________________________________________________________________________                              m)

Reference Example 116 Methyl 4-[4-[3-(4-Butylphenyl)-1-hydroxypropyl]phenyl]butyrate

To a solution of 4.40 g of methyl 4-[4-(4-butylcinnamoyl)phenyl]butyrate in 44 ml of methanol, 0.24 g of 10% palladium on carbon was added, and hydrogenation was carried out at an ordinary temperature and under ordinary pressure for 3.5 hours. After the catalyst was removed by filtration, 0.27 g of sodium borohydride was added to the filtrate under ice-cooling, and then stirring was continued at room temperature for 2 hours. After the reaction solvent was removed under reduced pressure, the residue was added with water and extracted with ether. The ether layer was washed with water, dried, and then the solvent was removed under reduced pressure to yield 4.34 g of colorless oil.

IR spectrum ν (liq) cm⁻¹ : 3432, 1740

Mass spectrum m/z: 368 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 0.92(3H,t,J=7.5 Hz), 1.34(2H,sex,J=7.5 Hz), 1.54-1.62(2H,m), 1.80(1H,brs), 1.95(2H,qn,J=7.5 Hz), 1.97-2.05(1H,m), 2.07-2.15(1H,m), 2.33(2H,t,J=7.5 Hz), 2.57(2H,t,J=7.5 Hz), 2.58-2.75(2H,m), 2.64(2H,t,J=7.5 Hz), 3.66(3H,s), 4.66(1H,brt,J=6.5 Hz), 7.05-7.12(4H,m), 7.16(2H,d,J=8 Hz), 7.27(2H,d,J=8 Hz)

Reference Example 117 Methyl 4-[4-[3-(4-Fluorophenyl)-1-hydroxypropyl]phenyl]butyrate

To a solution of 2.72 g of methyl 4-[4-(4-fluorocinnamoyl)phenyl]butyrate in 28 ml of methanol, 140 mg of 5% palladium on carbon was added, and hydrogenation was carried out at an ordinary temperature and under ordinary pressure for 4 hours. The catalyst was filtered off and then the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride→ethyl acetate) to yield 1.69 g of colorless oil.

IR spectrum ν (liq) cm⁻¹ : 3452, 1738

Mass spectrum m/z: 330 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.83(1H,brs), 1.91-2.14.(2H,m), 1.95(2H,qn,J=7.5 Hz), 2.33(2H,t,J=7.5 Hz), 2.60-2.75(2H,m), 2.64(2H,t,J=7.5 Hz), 3.66(3H,s), 4.63-4.65(1H,m), 6.95(2H,t,J=8.5 Hz), 7.13(2H,dd,J=8.5,5.5 Hz), 7.16(2H,d,J=8 Hz), 7.26(2H,d,J=8 Hz)

The compounds of Reference Examples 118 through 120 were obtained in the same manner as described in Reference Examples 116 and 117.

Reference Example 118 Methyl 4-[4-[1-Hydroxy-3-(p-tolyl)propyl]phenyl]butyrate

Appearance colorless oil

IR spectrum ν (liq) cm⁻¹ : 3440, 1738

Mass spectrum m/z: 326 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.79(1H,brs), 1.95(2H,qn,J=7.5 Hz), 1.94-2.04(1H,m), 2.06-2.16(1H,m), 2.31(3H,s), 2.33(2H,t,J=7.5 Hz), 2.58-2.74(2H,m), 2.64(2H,t,J=7.5 Hz), 3.66(3H,s), 4.65(1H,dd,J=7.5,5 Hz), 7.08(4H,s), 7.16(2H,d,J=8.5 Hz), 7.27(2H,d,J=8.5 Hz)

Reference Example 119 Methyl 4-[4-[3-(3-Fluorophenyl)-1-hydroxypropyl]phenyl]butyrate

Appearance colorless oil

IR spectrum ν (liq) cm⁻¹ : 3464, 1738

Mass spectrum m/z: 330 (M⁺)

NMR spectrum δ (CDCl₃) ppm: 1.80(1H,brs), 1.95(2H,qn,J=7.5 Hz), 1.97-2.04(1H,m), 2.07-2.16(1H,m), 2.33(2H,t,J=7.5 Hz), 2.60-2.78(2H,m), 2.65(2H,t,J=7.5 Hz), 3.67(3H,s), 4.62-4.68(1H,m), 6.84-6.91(2H,m), 6.96(1H,d,J=8 Hz), 7.17(2H,d,J=8 Hz), 7.19-7.25(1H,m), 7.26(2H,d,J=8 Hz)

Reference Example 120 Methyl 4-[4-[3-(4-Chlorophenyl)-1-hydroxypropyl]phenyl]butyrate

Appearance colorless oil

IR spectrum ν (liq) cm⁻¹ : 3464, 1738

Mass spectrum m/z: 346, 348 (M⁺, 3:1)

NMR spectrum δ (CDCl₃) ppm: 1.81(1H,brs), 1.94-2.02(1H,m), 1.95(2H,qn,J=7.5 Hz), 2.05-2.14(1H,m), 2.33(2H,t,J=7.5 Hz), 2.59-2.75(2H,m), 2.64(2H,t,J=7.5 Hz), 3.66(3H,s), 4.64(1H,brt), 7.11(2H,d,J=8.5 Hz), 7.16(2H,d,J=8 Hz), 7.21-7.28(4H,m)

Reference Example 121 Methyl 4-[4-[1-Chloro-2-phenylethyl)phenyl]butyrate

To a solution of 3.49 g of methyl 4-[4-(1-hydroxy-2-Phenylethyl)phenyl]butyrate in 17 ml of benzene, 1.10 ml of thionyl chloride was added dropwise under ice-cooling, and then stirring was continued at room temperature for 1.5 hours. The reaction solvent was removed under reduced pressure, and the residue was dissolved in ether. The ether layer was washed with water and dried, and then the solvent was removed under reduced pressure to yield 3.30 g of pale yellow oil.

IR spectrum ν (liq) cm⁻¹ : 1738

Mass spectrum m/z: 316, 318 (M⁺, 3:1)

NMR spectrum δ (CDCl₃) ppm: 1.95(2H,qn,J=7.5 Hz), 2.32(2H,t,J=7.5 Hz), 2.64(2H,t,J=7.5 Hz), 3.32(1H,dd,J=14,8 Hz), 3.38(1H,dd,J=14,8 Hz), 3.66(3H,s), 5.03(1H,t,J=8 Hz), 7.08-7.16(4H,m), 7.18-7.27(5H,m)

The compounds of Reference Examples 122 through 173 shown in Tables 27 to 36 were obtained in the same manner as described in Reference Example 121.

                                      TABLE 27     __________________________________________________________________________     Reference     Example           Compound    IR ν                             NMR     No.   Appearance  (liq) cm.sup.-1                             δ (CDCl.sub.3)     __________________________________________________________________________     122   Methyl 3-[4-(1-Chloro-2-                       1738  2.62(2H, t, J=7.5Hz), 2.94(2H, t, J=7.5Hz),           phenylethyl)phenyl]-                             3.32(1H, dd, J=14, 7Hz), 3.37           propionate        (1H, dd, J=14, 8Hz), 3.67(3H, s), 5.02           pale brown oil    (1H, dd, J=8, 7Hz), 7.10-7.17(4H, m), 7.19-                             7.28(5H, m)                       1738  1.93(2H, qn, J=7.5Hz), 2.31(2H, t, J=     123   Methyl 4-[4-[1-Chloro-2-                             7.5(Hz), 2.64(2H, t, J=7.5Hz), 3.36(1H,           (2-fluorophenyl)ethyl]-                             dd, J=14, 6.5Hz), 3.40(1H, dd, J=14,           phenyl]butyrate   8Hz), 3.66(3H, s), 5.11(1H, dd, J=8,           pale brown oil    6.5Hz), 6.97-7.14(4H, m), 7.14(2H, d,                             J=8Hz), 7.30(2H, d, J=Hz)     124   Methyl 4-[4-[1-Chloro-2-                       1736  1.95(2H, qn, J=7.5Hz), 2.32(2H, t, J=           (3-fluorophenyl)ethyl]-                             7.5Hz), 2.64(2H, t, J=7.5Hz), 3.31(1,H           phenyl]butyrate   dd, J=14, 6.5Hz), 3.37(1H, dd, J=14,           pale brown oil    8Hz), 3.67(3H, s), 5.01(1H, dd, J=8,                             6.5Hz), 6.82(1H, d, J=10Hz), 6.88-6.96                             (2H, m), 7.14(2H, d, J=8Hz), 7.17-7.26                             (1H, m), 7.26(2H, d, J=8Hz)     125   Methyl 4-[4-[1-Chloro-                       1738  1.95(2H, qn, J=7.5Hz), 2.32(2H, t, J=           (4-fluorophenyl)ethyl]-                             7.5Hz), 2.64(2H, t, J=7.5Hz), 3.28(lH,           phenyl]butyrate   dd, J=14, 7.5Hz), 3.35(1H, dd, J=14,           pale brown oil    7.5Hz), 3.67(3H, s), 4.97(1H, t, J=7.5Hz),                             6.93(2H, t, J=8.5Hz), 7.05(2H,                             dd, J=8.5, 5Hz), 7.14(2H, d, J=8Hz),                             7.24(2H, d, J=8Hz)     126   Methyl 4-[4-[1-Chloro-2-                       1738  1.95(2H, qn, J=7.5Hz), 2.32(2H, t, J=           (4-chlorophenyl)ethyl]-                             7.5Hz), 2.64(2H, t, J=7.5Hz), 3.28(1H,           phenyl]butyrate   dd, J=14, 7Hz), 3.34(1H, dd, J=14, 7Hz),           pale brown oil    3.67(3H, s), 4.98(1H, t, J=7Hz),                             7.02(2H, d, J=8.5Hz), 7.14(2H, d, J=8Hz),                             7.21(2H, d, J=8.5Hz), 7.24(2H, d,                             J=8Hz)     127   Methyl 4-[4-[1-Chloro-2-                       1738  1.95(2H, qn, J=7.5Hz), 2.30(2H, t, J=           (p-tolyl)ethyl]phenyl]-                             7.5Hz), 2.32(3H, s), 2.64(2H, t, J=7.5Hz),           butyrate          3.31(2H, dd, J=8, 6.5Hz), 3.66           pale yellow oil   (3H, s), 5.01(1H, dd, J=8, 6.5Hz), 7.00                             (2H, d, J=8Hz), 7.06(2H, d, J=8Hz), 7.13                             (2H, d, J=8.5Hz), 7.23(2H, d, J=8.5Hz)     __________________________________________________________________________

                                      TABLE 28     __________________________________________________________________________     Reference     Example           Compound    IR ν                             NMR     No.   Appearance  (liq) cm.sup.-1                             δ (CDCl.sub.3)     __________________________________________________________________________     128   Methyl 4-[4-(1-Chloro-                       1738  1.84(3H, d, J=6.5Hz), 1.95(2H, qn, J=           ethyl)phenyl]butyrate                             7.5Hz), 2.33(2H, t, J=7.5Hz), 2.65(2H,           pale brown oil    t, J=7.5Hz), 3.66(3H, s), 5.08(1H,                             q, J=6.5Hz), 7.17(2H, d, J=8.5Hz), 7.35                             (2H, d, J=8.5Hz)     129   Methyl 4-[4-(1-Chloro-                       1740  0.99(3H, t, J=7.5Hz, 1.95(2H, qn, J=           propyl)phenyl]butyrate                             7.5Hz), 2.03-2.16(2H, m), 2.33(2H, t,           pale brown oil    J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.66                             (3H, s), 4.77(1H, t, J=7Hz), 7.16(2H,                             d, J=8Hz), 7.29(2H, d, J=8Hz)     130   Methyl 5-[4-(1-Chloro-2-                       1736  1.60-1.70(4H, m), 2.33(2H, t, J=7Hz),           phenylethyl)phenyl]-                             2.62(2H, t, J=7Hz), 3.33(1H, dd, 14,           valerate          7Hz), 3.38(IH, dd, J=14, 8Hz), 3.66           colorless oil     (3H, s), 5.03(IH, dd, J=8, 7Hz), 7.11-                             7.34(4H, m), 7.22-7.27(5H, m)     131   Methyl 4[4-(1-Chloro                       1738  0.93(3H, t, J=7.5Hz), 1.29-1.40(1H,           butyl)phenyl]butyrate                             m), 1.43-1.56(1H, m), 1.91-2.03(1H,           colorless oil     m), 1.95(2H, qn, J=7.5Hz), 2.06-2.15                             (1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                             t, J=7.5Hz), 3.66(3H, s), 4.85(1H,                             t, J=7.5Hz), 7.16(2H, d, J=8.5Hz),                             7.29(2H, d, J=8.5Hz)     132   Methyl 4-[4-(1-Chloro                       1740  0.89(3H, t, J=7Hz), 1.23-1.40(3H, m),           pentyl)9 phenyl]butyrate                             1.40-1.50(1H, m), 1.95(2H, qn, J=           pale yellow oil   7.5Hz), 1.97-2.06(1H, m), 2.07-2.18(1,H                             Hm), 2.33(2H, t, J=7.5Hz), 2.64(2H,                             t, J=7.5Hz), 3.66(3H, s), 4.83(IH, dd,                             , J=8, 7Hz), 7.16(2H, d, J=8Hz), 7.29                             (2H, d, J=8Hz)     133   Methyl 4-[4-(1-Chloro-                       1738  0.87(3H, t, J=7Hz), I.22-1.39(5H, m),           hexyl)phenyl]butyrate                             1.40-1.50(1H, m), 1.95(2H, qn, J=7.5Hz),           pale brown oil    1.96-2.05(1H, m), 2.06-2.16(1H,                             m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                             t, J=7.5Hz), 3.66(3H, s), 4.83(1H, dd,                             J=8, 7Hz), 7.16(2H, d, J=8Hz), 7.29                             (2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 29     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ0 (CDCl.sub.3)     __________________________________________________________________________     134   Methyl 4-[4-(1-Chloro-                        1740  0.88(3H, t, J=7Hz), 1.20-1.35(13H, m),           decyl)phenyl]butyrate                              1.40-1.50(1H, m), 1.95(2H, qn, J=7.5Hz),           pale yellow oil    1.95-2.04(1H, m), 2.10-2.15                              (1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                              t, J=7.5Hz), 3.66(3H, s), 4.83(1H, dd,                              J=8, 6.5Hz), 7.16(2H, d, J=8Hz), 7.29                              (2H, d, J=8Hz)     135   Methyl 4-[4-(1-Chloro-2-                        1738  0.86(3H, d, J=7Hz), 1.10(3H, d, J=7Hz),           methylpropyl)phenyl]-                              1.95(2H, qn, J=7.5Hz), 2.22(1H, m),           butyrate           2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=           pale yellow oil    7.5Hz), 3.66(3H, s), 4.61(1H, d, J=7Hz),                              7.14(2H, d, J=8Hz), 7.25(2H, d, J=                              8Hz)     136   Methyl 4-[4-(1-Chloro-3-                        1740  0.93(3H, d, J=7Hz), 0.94(3H, d, J=7Hz),           methylbutyl)phenyl]-                              1.69-1.77(1H, m), 1.83(1H, dt, J=           butyrate           14.5, 7Hz), 1.95(2H, qn, J=7.5Hz), 2.05           pale yellow oil    (1H, ddd, J=14.5, 8.5, 7Hz), 2.33(2H,                              t, J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                              (3H, s), 4.92(1H, dd, J=14.5, 7Hz),                              7.16(2H, d, J=8Hz), 7.30(2H, d, J=8Hz     137   Methyl 4-[4-(1-Chloro-4-                        1738  0.88(6H, d, J=7Hz), 1.13-1.20(1H, m),           methylpentyl)phenyl]-                              1.35-1.42(1H, m), 1.53-1.62(1H, m),           butyrate           1.96(2H, qn, J=7.5Hz), 2.00-2.15(2H,           pale yellow oil    m), 2.33(2H, t, J=7.5Hz), 2.65(2H,                              t, J=7.5Hz), 3.66(3H, s), 4.79(1H, dd,                              J=14, 6Hz), 7.16(2H, d, J=8Hz), 7.29                              (2H, d, J=8Hz)     138   Methyl 4-[4-(1-Chloro-3,3-                        1738  0.90(9H, s), 1.95(2H, qn, J=7.5Hz), 2.11           dimethylbutyl)phenyl]-                              (1H, dd, J=14.5, 6.5Hz), 2.19(1H,           butyrate           dd, J=14.5, 6.5Hz), 2.32(2H, t, J=7.5Hz),           pale yellow oil    2.64(2H, t, J=7.5Hz), 3.67(3H, s),                              4.97(1H, t, J=6.5Hz), 7.15(2H, d, J=                              8Hz), 7.30(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 30     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     139   Methyl 4-[4-(Chlorocyclo-                        1738  1.06-1.14(1H, m), 1.41-1.48(1H, m),           pentylmethyl)phenyl]-                              1.50-1.71(5H, m), 2.01-2.08(1H, m),           butyrate           1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           pale brown oil     7.5Hz), 2.56(1H, m), 2.64(2H, t, J=7.5Hz),                              3.66(3H, s), 4.64(1H, d, J=9Hz),                              7.14(2H, d, J=8Hz), 7.28(2H, d, J=8Hz     140   Methyl 4-[4-(Chlorocyclo-                        1738  0.82-0.94(1H, m), 1.00-1.30(4H, m),           hexylmethyl)phenyl]-                              1.38-1.70(4H, m), 1.75-1.99(2H, m),           butyrate           1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           pale yellow oil    7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.58(1H, d, J=8Hz), 7.14(2H, d,                              J=8Hz), 7.24(2H, d, J=8Hz)     141   Methyl 4-[4-(Chlorocyclo-                        1738  1.14-1.25(1H, m), 1.32-1.65(9H, m),           heptylmethyl)phenyl]-                              1.65-1.74(1H, m), 1.95(2H, qn, J=7.5Hz),           butyrate           1.96-2.06(1H, m), 2.06-2.15(1H,           pale brown oil     m), 2.33(2H, qn, J=7.5Hz), 2.64(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.73(1H, d,                              J=7.5Hz), 7.14(2H, d, J=8Hz), 7.26(2H,                              d, J=8Hz)     142   Methyl 4-[4-(1-Chloro-2-                        1738  1.06-1.20(2H, m), 1.45-1.54(2H, m),           cyclopentylethyl)phenyl]-                              1.56-1.66(2H, m), 1.74-1.83(2H, m),           butyrate           1.85(1H, dt, J=15, 7.5Hz), 1.95(2H, qn,           pale brown oil     J=7.5Hz), 2.02(1H, dt, J=15, 7.5Hz),                              2.15-2.21(1H, m), 2.33(2H, t, J=7.5Hz),                              2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.86(IH, t, J=7.5Hz), 7.16(2H, d,                              J=8Hz), 7.30(2H, d, J=8Hz)     143   Methyl 4-[4-(1-Chloro-2-                        1740  0.86-1.01(2H, m), 1.10-1.27(3H, m),           cyclohexylethyl)phenyl]-                              1.40-1.50(1H, m), 1.62-1.80(5H, m),           butyrate           1.84(1H, dt, J=14, 7Hz), 1.95(2H, qn,           pale yellow oil    J=7.5Hz), 2.04(1H, ddd, J=14, 8.5, 6Hz,                              2.33(2H, t, J=7.5Hz), 2.64(2H, t,                              J=7.5Hz), 3.66(3H, s), 4.96(1H, dd, J=                              8.5, 7Hz), 7.16(2H, d, J=8Hz), 7.29                              (2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 31     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     144   Methyl 4-[4-(1-Chloro-3-                        1738  0.81-0.93(2H, m), 1.07-1.28(5H, m),           cyclohexylpropyl)phenyl]-                              1.32-1.42(1H, m), 1.58-1.76(5H, m),           butyrate           1.95(2H, qn, J=7.5Hz), 1.97-2.17(2H,           pale brown oil     m), 2.33(2H, t, J=7.5Hz), 2.64(2H, t,                              J=7.5Hz), 3.66(3H, s), 4.79(1H, t, J=                              7.5Hz), 7.15(2H, d, J=8Hz), 7.28(2H,                              d, J=8Hz)     145   Methyl 4-[4-(1-Chloro-4-                        1740  0.80-0.90(2H, m), 1.08-1.33(7H, m),           cyclohexylbutyl)phenyl]-                              1.44-1.52(1H, m), 1.59-1.72(5H, m),           butyrate           1.92-2.03(1H, m), I.95(2H, qn, J=7.5Hz),           pale brown oil     2.05-2.15(1H, m), 2.33(2H, t, J=                              7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66(3H,                              s), 4.83(IH, dd, J=8.5, 6.5Hz), 7.16                              (2H, d, J=8Hz), 7.29(2H, d, J=8Hz)     146   Methyl 4-[4-(1-Chloro-5-                        1740  0.80-0.88(2H, m), 1.08-1.34(9H, m),           cyclohexylpentyl)phenyl]-                              1.40-1.48(1H, m), 1.60-1.72(5H, m),           butyrate           1.95(2H, qn, J=7.5Hz), 1.95-2.05(1H,           pale brown oil     m), 2.08-2.15(1H, m), 2.33(2H, t, J=                              7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.83(1H, t, J=7Hz), 7.16(2H, d,                              J=8Hz), 7.29(2H, d, J=8Hz)     147   Methyl 4-[4-(1-Chloro-6-                        1738  0.79-0.90(2H, m), 1.10-1.55(12H, m),           cyclohexylhexyl)phenyl]-                              1.59-1.72(5H, m), 1.95(2H, qn, J=7.5Hz),           butyrate           1.97-2.16(2H, m), 2.33(2H, t, J=           pale yellow oil    7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66                              (3H, s), 4.83(1H, t, J=7.5Hz), 7.15(2H,                              d, J=8Hz), 7.29(2H, d, J=8Hz)     148   Methyl trans-4-[4-                        1740  0.79-0.98(3H, m), 0.86(3H, d, J=6.5Hz),           [Chloro-(4-methylcyclo-                              1.02-1.12(1H, m), 1.24-1.33(1H,           hexyl)methyl]phenyl]-                              m), 1.38-1.50(1H, m), 1.60-1.66(1H,           butyrate           m), 1.70-1.85(2H, m), 1.95(2H, qn, J=           pale yellow oil    7.5Hz), 2.18-2.24(1H, m), 2.33(2H, t,                              J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.67                              (3H, s), 4.57(1H, d, J=8Hz), 7.14(2H,                              d, J=8.5Hz), 7.23(2H, d, J=8.5Hz)     __________________________________________________________________________

                                      TABLE 32     __________________________________________________________________________     Reference     Example           Compound     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     149   Methyl trans-4-[4-                         1742  0.78-1.32(13H, m), 0.87(3H, t, J=7Hz),           [Chloro(4-pentylcyclo-                               1.40-1.47(IH, m), 1.65-1.71(1H, m),           hexyl)methyl]phenyl]-                               1.77-1.86(2H, m), 1.95(2H, qn, J=7.5Hz),           butyrate            2.18-2.25(1H, m), 2.33(2H, t,           pale yellow oil     J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66                               (3H, s), 4.57(1H, d, J=8Hz), 7.14(2H,                               d, J=8Hz), 7.23(2H, d, J=8Hz)     150   Methyl 4-[4-[2-(1-                         1738  1.44-1.68(13H, m), 1.93-1.97(5H, m),           Adamantyl)-1-chloroethyl]-                               1.98(1H, dd, J=14, 6.5Hz), 2.07(1H,           phenyl]butyrate     dd, J=14, 6.5Hz), 2.32(2H, t, J=7.5Hz),           pale yellow oil     2.64(2H, t, J=7.5Hz), 3.66(3H, s),                               5.04(1H, t, J=6.5Hz), 7.14(2H, d, J=8.5Hz),                               7.29(2H, d, J=8.5Hz)     151   Methyl 4-[4-[1-Chloro-2-                         1738  1.01-1.16(4H, m), 1.27-1.29(1H, m),           (2-norbornyl)ethyl]phenyl]-                               1.42-1.52(4H, m), 1.72-1.77(1H, m),           butyrate            1.94(2H, m), 1.94-2.02(2H, m), 2.12-           pale brown oil      2.20(1H, m), 2.33(2H, t, J=7.5Hz), 2.64                               (2H, t, J=7.5Hz), 3.66(3H, s), 4.84                               (1H, m), 7.16(2H, d, J=8Hz), 7.28(2H,                               d, J=8Hz)     152   Methyl 4-[4-(1-Chloro-3-                         1738  1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           phenylpropyl)phenyl]-                               7.5Hz), 2.28-2.36(1H, m), 2.40-2.49           butyrate            (1H, m), 2.65(2H, t, J=7.5Hz), 2.68-2.75           pale brown oil      (1H, m), 2.80(1H, ddd, J=14, 9, 5.5Hz),                               3.66(3H, s), 4.80(IH, dd, J=9, 5.5Hz),                               7.17-7.23(5H, m), 7.27-7.31(4H, m)     153   Methyl 5-[4-(1-Chloro-                         1738  0.89(3H, t, J=7Hz), 1.24-1.40(3H, m),           pentyl)phenyl]valerate                               1.40-1.51(1H, m), 1.60-1.73(4H, m),           pale yellow oil     1.97-2.07(1H, m), 2.07-2.18(1H, m),                               2.33(2H, t, J=7Hz), 2.62(2H, t, J=7Hz),                               3.66(3H, s), 4.83(1H, brt, J=7Hz),                               7.15(2H, d, J=8.5Hz), 7.28(2H, d, J=                               8.5Hz)     __________________________________________________________________________

                                      TABLE 33     __________________________________________________________________________     Reference     Example           Compound    IR ν                             NMR     No.   Appearance  (liq) cm.sup.-1                             δ (CDCl.sub.3)     __________________________________________________________________________     154   Methyl 5-[4-(1-Chloro-                       1740  0.85-0.90(3H, m), 1.22-1.39(5H, m),           hexyl)phenyl]valerate                             1.41-1.55(1H, m), 1.60-1.72(4H, m),           pale yellow oil   1.97-2.06(1H, m), 2.06-2.17(1H, m),                             2.33(2H, t, J=7Hz), 2.62(2H, t, J=7.5                             Hz), 3.66(3H, s), 4.83(1H, dd, J=8, 7H                             z), 7.15(2H, d, J=8.5Hz), 7.28(2H, d,                             J=8.5Hz)     155   Methyl 5-[4-(1-Chloro-2-                       1740  0.85-1.02(2H, m), 1.09-1.28(3H, m),           cyclohexylethyl)phenyl]-                             1.40-1.50(1H, m), 1.60-1.81(9H, m),           valerate          1.80-1.88(1H, m), 2.04(1H, ddd, J=14           pale brown oil    , 9, 6Hz), 2.33(2H, t, J=7Hz), 2.62(2H                             t, J=7Hz), 3.66(3H, s), 4.96(1H, dd,                             J=9, 6Hz), 7.15(2H, d, J=8Hz), 7.28(2                             H, d, J=8Hz)     156   Methyl 4-[4-(1-Chloro-                       1740  0.87(3H, t, J=7Hz), 1.22-1.34(7H, m.)           heptyl)phenyl]butyrate                             1.43-1.50(1H, m), 1.95(2H, qn, J=7.           pale brown oil    5Hz), 1.95-2.05(1H, m), 2.08-2.16(l                             H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                             t, J=7.5Hz), 3.67(3H, s), 4.83(1H, t,                             J=7Hz), 7.16(2H, d, J=8Hz), 7.29(2H,                             d, J=8Hz)     157   Methyl 4-[4-(1-Chloro-                       1740  0.87(3H, t, J=7Hz), 1.20-1.33(9H, m)           octyl)phenyl]butyrate                             1.42-1.50(1H, m), 1.95(2H, qn, J=7.           pale brown oil    5Hz), 1.95-2.05(1H, m), 2.08-2.26(l                             H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                             t, J=7.5Hz), 3.63(3H, s), 4.83(1H, dd                             , J=8, 7Hz), 7.16(2H, d, J=8Hz), 7.29                             2H, d, J=8Hz)     158   Methyl 4-[4-(1-Chloro-                       1740  0.87(3H, t, J=7Hz), 1.18-1.34(11H, m           nonyl)phenyl]butyrate                             ), 1.42-1.50(1H, m), 1.95(2H, qn, J=7           pale brown oil    .5Hz), 1.95-2.05(1H, m), 2.07-2.15                             1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H                             , t, J=7.5Hz), 3.66(3H, s), 4.83(1H, d                             d, J=8, 7Hz), 7.16(2H, d, J=8Hz), 7.29                             (2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 34     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     159   Methyl 4-[4-(1-Chloro-5-                        1740  0.85(3H, d, J=7Hz), 0.86(3H, d, J=7Hz),           methylhexyl)phenyl]-                              1.16-1.25(2H, m), 1.25-1.35(1H, m),           butyrate           1.44-1.58(2H, m), 1.95(2H, qn, J=7.5Hz),           pale brown oil     1.93-2.03(1H, m), 2.06-2.14                              (1H, m), 2.33(2H, t, J=7.5Hz), 2.64(2H,                              t, J=7.5Hz), 3.66(3H, s), 4.84(1H, dd,                              J=8, 6.5Hz), 7.16(2H, d, J=8Hz), 7.29(2H,                              d, J=8Hz)     160   Methyl 4-[4-(1-Chloro-6-                        1740  0.85(6H, d, J=6.5Hz), 1.12-1.19(2H,           methylheptyl)phenyl]-                              m), 1.23-1.35(3H, m), 1.40-1.55(2H,           butyrate           m), 1.95(2H, qn, J=7.5Hz), 1.95-2.06           pale brown oil     (1H, m), 2.07-2.16(1H, m), 2.33(2H, t,                              J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66(3H,                              s), 4.83(1H, t, J=7.5Hz), 7.16(2H,                              d, J=8Hz), 7.29(2H, d, J=8Hz)     161   Methyl 4-[4-(1-Chloro-4,4-                        1742  0.88(9H, s), 1.10(1H, td, J=13, 4.5Hz),           dimethylpentyl)phenyl]-                              1.43(1H, td, J=13, 4.5Hz), 1.96(2H,           butyrate           qn, J=7.5Hz), 1.95-2.13(2H, m), 2.34(2H,           pale brown oil     t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),                              3.67(3H, s), 4.77(1H, t, J=7.5Hz),                              7.16(2H, d, J=8.5Hz), 7.29(2H, d, J=                              8.5Hz)     162   Methyl 4-[4-(1-Chloro-5,5-                        1740  0.85(9H, s), 1.15-1.23(2H, m), 1.24-           dimethylhexyl)phenyl]-                              1.35(1H, m), 1.40-1.51(1H, m), 1.91-           butyrate           2.00(1H, m), 1.95(2H, qn, J=7.5Hz), 2.04-           pale brown oil     2.13(1H, m), 2.33(2H, t, J=7.5Hz),                              2.65(2H, t, J=7.5Hz), 3.66(3H, s),                              4.85(1H, dd, J=8.5, 6Hz), 7.16(2H, d,                              J=8.5Hz), 7.29(2H, d, J=8.5Hz)     163   Methyl 4-[4-(1-Chloro-6,6-                        1742  0.85(9H, s), 1.11-1.16(2H, m), 1.21-           dimethylheptyl)phenyl]-                              1.30(3H, m), 1.37-1.49(1H, m), 1.94-           butyrate           2.06(1H, m), 1.95(2H, qn, J=7.5Hz), 2.07-           pale brown oil     2.17(1H, m), 2.33(2H, t, J=7.5Hz),                              2.64(2H, t, J=7.5Hz), 3.66(3H, s),                              4.83(1H, dd, J=8, 6Hz), 7.16(2H, d, J=                              8Hz), 7.29(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 35     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     164   Methyl 4-[4-(1-Chloro-3-                        1740  1.00-1.10(2H, m), 1.25-1.35(1H, m),           cyclopentylpropyl)phenyl]-                              1.45-1.65(5H, m), 1.70-1.80(3H, m),           butyrate           1.96(2H, qn, J=7.5Hz), 2.00-2.15(2H,           pale brown oil     m), 2.33(2H, t, J=7.5Hz), 2.65(2H, t,                              J=7.5Hz), 3.67(3H, s), 4.82(1H, t, J=                              7.5Hz), 7.16(2H, d, J=8Hz), 7.29(2H,                              d, J=8Hz)     165   Methyl 4-[4-[3-(4-Butoxy-                        1738  0.97(3H, t, J=7.5Hz), 1.49(2H, sex, J=           phenyl)-1-chloropropyl]-                              7.5Hz), 1.72-1.79(1H, m), 1.95(2H,           phenyl]butyrate    qn, J=7.5Hz), 2.23-2.35(1H, m), 2.33(2H,           pale violet oil    t, J=7.5Hz), 2.36-2.45(1H, m), 2.60-                              2.76(2H, m), 2.64(2H, t, J=7.5Hz),                              3.66(3H, s), 3.94(2H, t, J=7Hz), 4.78(1H,                              dd, J=8.5, 6Hz), 6.82(2H, d, J=                              8.5Hz), 7.08(2H, d, J=8.5Hz), 7.16(2H,                              d, J=8Hz), 7.27(2H, d, J=8Hz)     166   Methyl 4-[4-(1-Chloro-4-                        1738  1.60-1.69(1H, m), 1.78-1.88(1H, m),           phenylbutyl)phenyl]-                              1.95(2H, qn, J=7.5Hz), 2.01-2.09(1H,           butyrate           m), 2.11-2.20(1H, m), 2.33(2H, t, J=           pale yellow oil    7.5Hz), 2.64(4H, t, J=7.5Hz), 3.66(3H,                              s), 4.84(1H, dd, J=8.5, 6.5Hz), 7.13-                              7.20(5H, m), 7.24-7.29(4H, m)     167   Methyl 4-[4-(1-Chloro-5-                        1738  1.32-1.42(1H, m), 1.50-1.68(3H, m),           phenylpentyl)phenyl]-                              1.95(2H, qn, J=7.5Hz), 2.00-2.08(1H,           butyrate           m), 2.10-2.19(1H, m), 2.33(2H, t, J=           pale yellow oil    7.5Hz), 2.60(2H, t, J=7.5Hz), 2.64(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.82(1H,                              t, J=8Hz), 7.13-7.20(5H, m), 7.24-7.29(4H, m)     168   Methyl 4-[4-(1-Chloro-6-                        1738  1.28-1.65(6H, m), 1.90-2.05(1H, m),           phenylhexyl)phenyl]-                              1.95(2H, qn, J=7.5Hz), 2.06-2.15(1H,           butyrate           m), 2.33(2H, t, J=7.5Hz), 2.58(2H, t,           pale yellow oil    J=7.5Hz), 2.64(2H, t, J=7.5Hz), 3.66(3H,                              s), 4.81(1H, t), 7.12-7.19(3H,                              m), 7.15(2H, d, J=8Hz), 7.24-7.30(2H,                              m)7.27(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 36     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     169   Methyl 4-(4-[3-(4-Butyl-                        1740  0.92(3H, t, J=7.5Hz), 1.35(2H, sex, J=           phenyl)-1-chloropropyl]-                              7.5Hz), 1.54-1.62(2H, m), 1.95(2H,           phenyl]butyrate    qn, J=7.5Hz), 2.26-2.36(1H, m), 2.33(2H,           pale yellow oil    t, J=7.5Hz), 2.39-2.47(1H, m), 2.58(2H,                              t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                              2.63-2.71(1H, m), 2.76(1H, ddd,                              J=14, 9, 5.5Hz), 3.66(3H, s), 4.80(1H,                              dd, J=8.5, 6Hz), 7.06-7.12(4H, m),                              7.16(2H, d, J=8.5Hz), 7.28(2H, d, J=8.5Hz)     170   Methyl 4-[4-[1-Chloro-3-                        1738  1.95(2H, qn, J=7.5Hz), 2.25-2.35(1H,           (p-tolyl)propyl]phenyl]-                              m), 2.32(3H, s), 2.33(2H, t, J=7.5Hz),           butyrate           2.36-2.47(1H, m), 2.60-2.79(2H, m),           pale green oil     2.64(2H, t, J=7.5Hz), 4.79(1H, dd,                              J=8, 6Hz), 7.07(2H, d, J=8Hz), 7.10(2H,                              d, J=8Hz), 7.15(2H, d, J=8.5Hz), 7.28(2H,                              d, J=8.5Hz)     171   Methyl 4-[4-[1-Chloro-3-                        1738  1.95(2H, qn, J=7.5Hz), 2.24-2.46(2H,           (4-fluorophenyl)propyl]-                              m), 2.33(2H, t, J=7.5Hz), 2.65(2H, t,           phenyl]butyrate    J=7.5Hz), 2.68-2.72(1H, m), 2.74-2.81(1H,           colorless oil      m), 3.66(3H, s), 4.77(1H, dd,                              J=8.5, 6.5Hz), 6.97(2H, t, J=8.5Hz),                              7.13(2H, dd, J=8.5, 5.5Hz), 7.16(2H,                              d, J=8Hz), 7.27(2H, d, J=8Hz)     172   Methyl 4-[4-[1-Chloro-3-                        1738  1.95(2H, qn, J=7.5Hz), 2.28-2.35(1H,           (3-fluorophenyl)propyl]-                              m), 2.33(2H, t, J=7.5Hz), 2.39-2.47           phenyl]butyrate    (1H, m), 2.65(2H, t, J=7.5Hz), 2.68-2.75(1H,           colorless oil      m), 2.77-2.84(1H, m), 3.66(3H,                              s), 4.78(1H, dd, J=8.5, 5.5Hz), 6.87-                              6.96(3H, m), 7.17(2H, d, J=8Hz), 7.22-                              7.27(1H, m), 7.28(2H, d, J=8Hz)     173   Methyl 4-[4-[3-(4-Chloro-                        1738  1.95(2H, qn, J=7.5Hz), 2.24-2.34(1H,           phenyl)-1-chloropropyl]-                              m), 2.33(2H, t, J=7.5Hz), 2.37-2.46(1H,           phenyl]butyrate    m), 2.65(2H, t, J=7.5Hz), 2.66-2.72(1H,           pale yellow oil    m), 2.74-2.82(1H, m), 3.66(3H,                              s), 4.76(1H, dd, J=8.5, 6Hz), 7.11(2H,                              d, J=8.5Hz), 7.16(2H, d, J=8Hz), 7.23-                              7.30(4H, m)     __________________________________________________________________________

Reference Example 174 Methyl 4-[4-(1-Azido-2-phenylethyl)phenyl]butyrate

A suspension of 3.30 g of methyl 4-[4-(1-chloro-2-phenylethyl]phenyl]butyrate and 1.35 g of sodium azide in 15 ml of N,N-dimethylformamide was stirred at 100° C. for 3.5 hours. The reaction mixture was added with water and then extracted with ether. The ether layer was washed with water and dried, and then the solvent was removed under reduced pressure to yield 3.10 g of pale brown oil.

IR spectrum ν (liq) cm⁻¹ : 2104, 1738

NMR spectrum δ (CDCl₃) ppm: 1.96(2H,qn,J=7.5 Hz), 2.33(2H,t,J=7.5 Hz), 2.65(2H,t,J=7.5 Hz), 3.01(1H,dd,J=13.5,6 Hz), 3.66(1H,dd,J=13.5,8. 5 Hz), 3.67(3H,s), 4.63(1H,dd,J=8.5,6 Hz), 7.14-7.29(9H,m)

The compounds of Reference Examples 175 through 226 shown in Tables 37 to 45 were obtained in the same manner as described in Reference Example 174.

                                      TABLE 37     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     175   Methyl 3-[4-(1-Azido-2-                        2104, 2.63(2H, t, J=8Hz), 2.95(2H, t, J=8Hz),           phenylethyl)phenyl]-                        1738  3.00(1H, dd, J=14, 6Hz), 3.06(1H, dd,           propionate         J=14, 8.5Hz), 3.67(3H, s), 4.63(1H,           colorless oil      dd, J=8.5, 6Hz), 7.13-7.29(9H, m)     176   Methyl 4-[4-[1-Azido-2-                        2108, 1.96(2H, qn, J=7.5Hz), 2.33(2H, t, J=           (2-fluorophenyl)ethyl]-                        1738  7.5Hz), 2.65(2H, t, J=7.5Hz), 3.07(2H,           phenyl]butyrate    d, J=7.5Hz), 3.67(3H, s), 4.71(2H,           pale brown oil     d, J=7.5Hz), 6.99-7.30(4H, m), 7.17(2H,                              d, J=8.5Hz), 7.23(2H, d, J=8.5Hz)     177   Methyl 4-[4-[1-Azido-2-                        2104, 1.96(2H, qn, J=7.5Hz), 2.33(2H, t, J=           (3-fluorophenyl)ethyl]-                        1738  7.5Hz), 2.66(2H, t, J=7.5Hz), 2.99(1H,           phenyl]butyrate    dd, J=14, 6Hz), 3.05(1H, dd, J=14, 8.5Hz),           pale brown oil     3.67(3H, s), 4.63(1H, dd, J=8.5,                              6Hz), 6.84(1H, d, J=9.5Hz), 6.89-6.95(2H,                              m), 7.16-7.26(5H, m)     178   Methyl 4-[4-[1-Azido-2-                        2108, 1.96(2H, qn, J=7.5Hz), 2.33(2H, t, J=           (4-fluorophenyl)ethyl]-                        1738  7.5Hz), 2.66(2H, t, J=7.5Hz), 2.97(1H,           phenyl]butyrate    dd, J=14, 6Hz), 3.03(1H, dd, J=14, 8Hz),           pale brown oil     3.67(3H, s), 4.59(1H, dd, J=8, 6Hz),                              6.95(2H, t, J=8.5Hz), 7.08(2H, dd,                              J=8.5, 5.5Hz), 7.17(4H, s)     179   Methyl 4-[4-[1-Azido-2-                        2108, 1.96(2H, qn, J=7.5Hz), 2.33(2H, t, J=           (4-chlorophenyl)ethyl]-                        1738  7.5Hz), 2.65(2H, t, J=7.5Hz), 2.96(1H,           phenyl]butyrate    dd, J=14, 6Hz), 3.02(1H, dd, J=14, 8Hz),           pale brown oil     3.67(3H, s), 4.60(1H, dd, J=8, 6Hz),                              7.04(2H, d, J=8.5Hz), 7.17(4H, s),                              7.23(2H, d, J=8.5Hz)     180   Methyl 4-[4-[1-Azido-2-                        2104, 1.96(2H, qn, J=7.5Hz), 2.32(3H, s), 2.33(2H,           (p-tolyl)ethyl]phenyl]-                        1740  (2H, t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),           butyrate           2.97(1H, dd, J=14, 8.5Hz), 3.02(1H,           pale brown oil     dd, J=14, 8.5Hz), 3.67(3H, s), 4.60,                              4.61(1H, dd, J=8.5Hz), 7.03(2H, d,                              J=8Hz), 7.09(2H, d, J=8Hz), 7.18(2H,                              d, J=8Hz), 7.21(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 38     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     181   Methyl 4-[4-(1-Azidoethyl)-                         2108, 1.52(3H, d, J=6.5Hz), 1.96(2H, qn, J=           phenyl]butyrate                         1738  7.5Hz), 2.33(2H, t, J=7.5Hz), 2.65(2H,           pale brown oil      t, J=7.5Hz), 3.67(3H, s), 4.58(1H,                               q, J=6.5Hz), 7.19(2H, d, J=8Hz), 7.24(2H,                               d, J=8Hz)     182   Methyl 4-[4-(1-Azido-                         2104, 0.93(3H, t, J=7.5Hz), 1.74-1.89(2H,           propyl)phenyl]butyrate                         1738  m), 1.96(2H, qn, J=7.5Hz), 2.33(2H, t,           pale brown oil      J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.31(1H, t, J=7.5Hz), 7.18(2H,                               d, J=8Hz), 7.21(2H, d, J=8Hz)     183   Methyl 5-[4-(1-Azido-2-                         2104, 1.60-1.67(4H, m), 2.34(2H, t, J=7Hz),           phenylethyl)phenyl]-                         1736  2.63(2H, t, J=7Hz), 3.01(1H, dd, J=1.4,           valerate            6Hz), 3.06(1H, dd, J=14, 8.5Hz), 3.67(3H,           colorless oil       s), 4.63(1H, dd, J=8.5, 6Hz), 7.14-                               7.33(9H, m)     184   Methyl 4-[4-(1-Azidobutyl)-                         2100, 0.92(3H, t, J=7.5Hz), 1.24-1.47(2H,           phenyl]butyrate                         1738  m), 1.67-1.75(1H, m), 1.77-1.86(1H,           pale yellow oil     m), 1.96(2H, qn, J=7.5Hz), 2.34(2H, t,                               J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.38(1H, t, J=7.5Hz), 7.18(2H,                               d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     185   Methyl 4-[4-(1-Azido-                         2106, 0.89(3H, t, J=7Hz), 1.18-1.43(4H, m),           pentyl)phenyl]butyrate                         1738  1.67-1.77(1H, m), 1.78-1.88(1H, m),           pale brown oil      1.96(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),                               2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.36(1H, t, J=7.5Hz), 7.18(2H,                               d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     186   Methyl 4-[4-(1-Azidohexyl)-                         2100, 0.87(3H, t, J=7Hz), 1.20-1.35(5H, m),           phenyl]butyrate                         1738  1.33-1.45(1H, m), 1.67-1.77(1H, m),           colorless oil       1.77-1.87(1H, m), 1.96(2H, qn, J=7.5Hz),                               2.34(2H, t, J=7.5Hz), 2.65(2H,                               t, J=7.5Hz), 3.67(3H, s), 4.36(1H, t,                               J=7.5Hz), 7.18(2H, d, J=8Hz), 7.21(2H,                               d, J=8Hz)     187   Methyl 4-[4-(1-Azidodecyl)-                         2100, 0.87(3H, t, J=7Hz), 1.20-1.40(14H, m),           phenyl]butyrate                         1742  1.68-1.76(1H, m), 1.78-1.85(1H, m),           pale yellow oil     1.96(2H, qn, J=7.5Hz), 2.34(2H, t,                               J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.34-4.37(1H, m), 7.18(2H, d,                               J=8Hz), 7.21(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 39     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     188   Methyl 4-[4-(1-Azido-2-                        2104, 0.78(3H, d, J=7Hz), 1.01(3H, d, J=7Hz),           methylpropyl)phenyl]-                        1738  1.92-2.01(1H, m), 1.97(2H, qn, J=7.5Hz),           butyrate           2.34(2H, t, J=7.5Hz), 2.65(2H,           pale yellow oil    t, J=7.5Hz), 3.67(3H, s), 4.10(1H, d,                              J=8.5Hz), 7.17(4H, s)     189   Methyl 4-[4-(1-Azido-3-                        2104, 0.93(6H, d, J=6.5Hz), 1.56(1H, dt, J=           methylbutyl)phenyl]-                        1740  13.5, 6.5Hz), 1.60-1.68(1H, m), 1.75(1H,           butyrate           ddd, J=13.5, 9, 6.5Hz), 1.96(2H,           colorless oil      qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz), 2.65(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.43(1H,                              dd, J=9, 6.5Hz), 7.18(2H, d, J=8Hz),                              7.22(2H, d, J=8Hz)     190   Methyl 4-[4-(1-Azido-4-                        2100, 0.87(3H, d, J=7Hz), 0.88(3H, d, J=7Hz),           methylpentyl)phenyl]-                        1740  1.10-1.17(1H, m), 1.26-1.33(1H, m),           butyrate           1.50-1.59(1H, m), 1.70-1.86(2H, m),           pale yellow oil    1.96(2H, qn, J=7.5Hz), 2.34(2H, t,                              J=7.5Hz), 2.66(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.32(1H, t, J=7Hz), 7.18(2H,                              d, J=8Hz), 7.21(2H, d, J=8Hz)     191   Methyl 4-[4-(1-Azido-3,3-                        2104, 0.95(9H, s), 1.65(1H, dd, J=14.5, 5Hz),           dimethylbutyl)phenyl]-                        1738  1.81(1H, dd, J=14.5, 8.5Hz), 1.96(2H,           butyrate           qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),           colorless oil      2.65(2H, t, J=7.5Hz), 3.67(3H, s),                              4.42(1H, dd, J=8.5, 5Hz), 7.18(2H, d,                              J=8.5Hz), 7.22(2H, d, J=8.5Hz)     192   Methyl 4-[4-(Azidocyclo-                        2100, 1.05-1.14(1H, m), 1.48-1.54(3H, m),           pentylmethyl)phenyl]-                        1740  1.54-1.69(3H, m), 1.88-1.93(1H, m),           butyrate           1.96(2H, qn, J=7.5Hz), 2.27(1H, m), 2.34(2H,           pale brown oil     t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),                              3.67(3H, s), 4.12(1H, d, J=9Hz),                              7.17(2H, d, J=8Hz), 7.21(2H, d, J=8Hz)     193   Methyl 4-[4-(Azidocyclo-                        2100, 0.82-0.94(1H, m), 0.96-1.28(4H, m),           hexylmethyl)phenyl]-                        1740  1.33-1.40(1H, m), 1.56-1.69(3H, m),           butyrate           1.72-1.80(1H, m), 1.92-2.02(1H, m),           pale yellow oil    1.97(2H, qn, J=7.5Hz), 2.34(2H, t, J=                              7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.11(1H, d, J=7.5Hz), 7.16(2H,                              s), 7.17(2H, s)     __________________________________________________________________________

                                      TABLE 40     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     194   Methyl 4-[4-(Azidocyclo-                        2104, 1.06-1.16(1H, m), 1.24-1.40(2H, m),           heptylmethyl)phenyl]-                        1740  1.36-1.64(7H, m), 1.64-1.74(1H, m),           butyrate           1.81-1.95(2H, m), 1.97(2H, qn, J=7.5Hz),           pale brown oil     2.34(2H, t, J=7.5Hz), 2.65(2H, t,                              J=7.5Hz), 3.67(3H, s), 4.20(1H, d, J=                              8Hz), 7.17(4H, s)     195   Methyl 4-[4-(1-Azido-2-                        2100, 1.08-1.20(2H, m), 1.46-1.54(2H, m),           cyclopentylethyl)phenyl]-                        1738  1.57-1.65(2H, m), 1.70-1.83(4H, m),           butyrate           1.84-1.90(1H, m), 1.96(2H, qn, J=7.5Hz),           pale yellow oil    2.34(2H, t, J=7.5Hz), 2.65(2H, t,                              J=7.5Hz), 3.67(3H, s), 4.38(1H, t, J=7.5Hz),                              7.18(2H, d, J=8Hz), 7.22(2H,                              d, J=8Hz)     196   Methyl 4-[4-(1-Azido-2-                        2100, 0.85-1.00(2H, m), 1.10-1.27(3H, m),           cyclohexylethyl)phenyl]-                        1740  1.33-1.40(1H, m), 1.56(1H, qn, J=7Hz),           butyrate           1.61-1.80(6H, m), 1.96(2H, qn, J=7.5Hz),           pale yellow oil    2.34(2H, t, J=7.5Hz), 2.65(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.47(1H, dd,                              J=8.5, 6Hz), 7.18(2H, d, J=8Hz), 7.21(2H,                              d, J=8Hz)     197   Methyl 4-[4-(1-Azido-3-                        2100, 0.80-0.92(2H, m), 1.06-1.34(6H, m),           cyclohexylpropyl)phenyl]-                        1740  1.59-1.72(5H, m), 1.69-1.87(2H, m),           butyrate           1.96(2H, qn, J=7.5Hz), 2.34(2H, t, J=           pale brown oil     7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.32(1H, t, J=7.5Hz), 7.18(2H,                              d, J=8Hz), 7.20(2H, d, J=8Hz)     198   Methyl 4-[4-(1-Azido-4-                        2100, 0.79-0.90(2H, m), 1.09-1.30(7H, m),           cyclohexylbutyl)phenyl]-                        1738  1.35-1.44(1H, m), 1.60-1.73(6H, m),           butyrate           1.76-1.84(1H, m), 1.96(2H, qn, J=7.5Hz),           pale brown oil     2.34(2H, t, J=7.5Hz), 2.65(2H, t,                              J=7.5Hz), 3.67(3H, s), 4.36(1H, t, J=                              7.5Hz), 7.18(2H, d, J=8.5Hz), 7.21(2H,                              d, J=8.5Hz)     199   Methyl 4-[4-(1-Azido-5-                        2100, 0.80-0.88(2H, m), 1.08-1.40(10H, m)           cyclohexylpentyl)phenyl]-                        1742  1.60-1.75(6H, m), 1.78-1.86(1H, m),           butyrate           1.96(2H, qn, J=7.5Hz), 2.34(2H, t, J=           pale yellow oil    7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.36(1H, t, J=7Hz), 7.18(2H, d,                              J=8.5Hz), 7. 21(2H, d, J=8.15Hz)     __________________________________________________________________________

                                      TABLE 41     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     200   Methyl 4-[4-(1-Azido-6-                         2100, 0.79-0.92(2H, m), 1.08-1.44(12H, m)           cyclohexylhexyl)phenyl]-                         1742  1.60-1.86(7H, m), 1.96(2H, qn, J=7.5Hz),           butyrate            2.34(2H, t, J=7.5Hz), 2.65(2H,           pale brown oil      t, J=7.5Hz), 3.67(3H, s), 4.36(1H, t,                               J=7.5Hz), 7.18(2H, d, J=8Hz), 7.21(2H,                               d, J=8Hz)     201   Methyl trans-4-[4-                         2100, 0.76-1.08(4H, m), 0.85(3H, d, J=6Hz),           [Azido(4-methylcyclohexyl)-                         1738  1.18-1.38(2H, m), 1.50-1.65(2H, m),           methyl]phenyl]butyrate                               1.70-1.76(1H, m), 1.97(2H, qn, J=7.5Hz),           pale yellow oil     1.97-2.04(1H, m), 2.34(2H, t, J=                               7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               3H, s), 4.09(1H, d, J=8.5Hz), 7.15(2H,                               d, J=8.5Hz), 7.17(2H, d, J=8.5Hz)     202   Methyl trans-4-[4-                         2100, 0.74-1.41(14H, m), 0.87(3H, t, J=7.5Hz),           (Azido(4-pentylcyclohexyl)-                         1742  1.52-1.61(1H, m), 1.64-1.70(1H,           methyl]phenyl]butyrate                               m), 1.76-1.82(1H, m), 1.97(2H, qn, J=           pale yellow viscous oil                               7.5Hz), 1.98-2.04(1H, m), 2.34(2H,                               t, J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.09(1H, d, J=8Hz), 7.16(2H,                               d, J=6Hz), 7.17(2H, d, J=6Hz)     203   Methyl 4-[4-[2-(1-                         2104, 1.45-1.74(15H, m), 1.91-1.98(4H, m),           Adamantyl)-1-azidoethyl]-                         1740  2.33(2H, t, J=7.5Hz), 2.65(2H, t, J=           phenyl]butyrate     7.5Hz), 3.67(3H, s), 4.47(1H, dd, J=8,           pale yellow oil     4Hz), 7.17(2H, d, J=8Hz), 7.21(2H, d,                               J=8Hz)     204   Methyl 4-[4-[1-Azido-2-(2-                         2100, 1.03-1.16(4H, m), 1.22-1.30(1H, m),           norbornyl)ethyl]phenyl]-                         1740  1.43-1.54(5H, m), 1.60-1.71(1H, m),           butyrate            1.93-1.99(3H, m), 2.20(1H, s), 2.34           pale yellow oil     2H, t, J=7.5Hz), 2.65(2H, t, J=7.5Hz)                               3.67(3H, s), 4.36(1H, m), 7.18(2H, d,                               J=8Hz), 7.20(2H, d, J=8Hz)     205   Methyl 4-[4-(1-Azido-3-                         2100, 1.96(2H, qn, J=7.5Hz), 2.00-2.08(1H,           phenylpropyl)phenyl]-                         1738  m), 2.10-2.19(1H, m), 2.34(2H, t, J=           butyrate            7.5Hz), 2.61-2.74(2H, m), 2.66(2H, t,           pale brown oil      J=7.5Hz), 3.67(3H, s), 4.37(1H, dd,                               J=8.5, 6Hz), 7.14-7.23(7H, m), 7.29(2H,                               t, J=7.5Hz)     __________________________________________________________________________

                                      TABLE 42     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     206   Methyl 5-[4-(1-Azido-                         2100, 0.88(3H, t, J=7.5Hz), 1.18-1.42(4H,           pentyl)phenyl]valerate                         1740  m), 1.60-1.90(6H, m), 2.34(2H, t, J=7Hz),           pale brown oil      2.63(2H, t, J=7Hz), 3.66(3H, s),                               4.36(1H, brt, J=7.5Hz), 7.17(2H, d, J=                               8.5Hz), 7.20(2H, d, J=8.5Hz)     207   Methyl 5-[4-(1-Azidohexyl)-                         2100, 0.87(3H, t, J=7Hz), 1.21-1.46(6H, m),           phenyl]valerate                         1740  1.61-1.88(6H, m), 2.34(2H, t, J=7Hz),           pale brown oil      2.63(2H, t, J=7Hz), 3.66(3H, s), 4.36(1H,                               t, J=7Hz), 7.17(2H, d, J=8.5Hz),                               7.20(2H, d, J=8.5Hz)     208   Methyl 5-[4-(1-Azido-2-                         2100, 0.87-1.00(2H, m), 1.09-1.28(3H, m),           cyclohexylethyl)phenyl]-                         1740  1.29-1.41(1H, m), 1.51-1.80(11H, m),           valerate            2.34(2H, t, J=7Hz), 2.63(2H, t, J=7.5Hz),           pale brown oil      3.67(3H, s), 4.46(1H, dd, J=9, 6Hz),                               7.17(2H, d, J=8.5Hz), 7.20(2H, d,                               J=8.5Hz)     209   Methyl 4-[4-(1-Azido-                         2100, 0.87(3H, t, J=7Hz), 1.20-1.41(8H, m),           heptyl)phenyl]butyrate                         1740  1.68-1.77(1H, m), 1.78-1.86(1H, m),           pale yellow oil     1.96(2H, qn, J=7.5Hz), 2.34(2H, t, J=                               7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.36(1H, t, J=7Hz), 7.18(2H, d,                               J=8.5Hz), 7.21(2H, d, J=8.5Hz)     210   Methyl 4-[4-(1-Azidooctyl)-                         2100, 0.87(3H, t, J=7Hz), 1.20-1.43(10H, m),           phenyl]butyrate                         1742  1.68-1.76(1H, m), 1.79-1.86(1H, m),           pale yellow oil     1.96(2H, qn, J=7.5Hz), 2.34(2H, t,                               J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.36(1H, t, J=7.5Hz), 7.18(2H,                               d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     211   Methyl 4-[4-(1-Azidononyl)-                         2100, 0.87(3H, t, J=7Hz), 1.19-1.42(12H, m),           phenyl]butyrate                         1740  1.67-1.75(1H, m), 1.78-1.86(1H, m),           pale yellow oil     1.96(2H, qn, J=7.5Hz), 2.34(2H, t,                               J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                               s), 4.36(1H, t, J=7Hz), 7.18(2H,                               d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     __________________________________________________________________________

                                      TABLE 43     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     212   Methyl 4-[4-(1-Azido-5-                        2100, 0.85(3H, d, J=7Hz), 0.85(3H, d, J=7Hz),           methylhexl)phenyl]-                        1738  1.16-1.20(2H, m), 1.21-1.31(1H, m),           butyrate           1.34-1.44(1H, m), 1.46-1.55(1H, m),           pale yellow oil    1.65-1.73(1H, m), 1.76-1.84(1H, m),                              1.96(2H, qn, J=7.5Hz), , 2.34(2H, t,                              J=7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.37(1H, t, J=7.5Hz), 7.18(2H,                              d, J=8Hz), 7.21(2H, d, J=8Hz)     213   Methyl 4-[4-(1-Azido-6-                        2100, 0.85(6H, d, J=7Hz), 1.08-1.20(2H, m),           methylheptyl)phenyl]-                        1742  1.20-1.40(4H, m), 1.42-1.57(1H, m),           butyrate           1.66-1.77(1H, m), 1.77-1.87(1H, m),           pale brown oil     1.96(2H, qn, J=7.5Hz), 2.34(2H, t, J=                              7.5Hz), 2.65(2H, t, J=7.5Hz), 3.67(3H,                              s), 4.36(1H, t, J=7.5Hz), 7.18(2H,                              d, J=8Hz), 7.21(2H, d, J=8Hz)     214   Methyl 4-[4-(1-Azido-4,4-                        2100, 0.87(9H, s), 1.10(1H, td, J=13, 5Hz),           dimethylpentyl)phenyl]-                        1740  1.34(1H, td, J=13, 5Hz), 1.66-1.83(2H,           butyrate           m), 1.97(2H, qn, J=7.5Hz), 2.34(2H,           pale yellow oil    t, J=7.5Hz), 2.66(2H, t, J=7.5Hz),                              3.67(3H, s), 4.30(1H, t, J=7Hz), 7.19(2H,                              d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     215   Methyl 4-(4-(1-Azido-5,5-                        2104, 0.85(9H, s), 1.14-1.28(3H, m), 1.31-           dimethylhexyl)phenyl]-                        1740  1.42(1H, m), 1.64-1.72(1H, m), 1.74-           butyrate           1.84(1H, m), 1.96(2H, qn, J=7.5Hz), 2.33(2H,           pale yellow oil    t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),                              3.67(3H, s), 4.38(1H, dd, J=8, 6Hz),                              7.18(2H, d, J=8.5Hz), 7.21(2H, d,                              J=8.5Hz)     216   Methyl 4-[4-(1-Azido-6,6-                        2100, 0.85(9H, s), 1.10-1.16(2H, m), 1.18-           dimethylhexyl)phenyl]-                        1742  1.39(4H, m), 1.69-1.76(1H, m), 1.79-           butyrate           1.89(1H, m), 1.96(2H, qn, J=7.5Hz), 2.34(2H,           pale brown oil     t, J=7.5Hz), 2.65(2H, t, J=7.5Hz),                              3.67(3H, s), 4.36(1H, t, J=7Hz),                              7.18(2H, d, J=8.5Hz), 7.21(2H, d, J=                              8.5Hz)     __________________________________________________________________________

                                      TABLE 44     __________________________________________________________________________     Reference     Example           Compound     I R ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     217   Methyl 4-[4-(1-Azido-3-                        2100, 1.00-1.10(2H, m), 1.20-1.30(1H, m),           cyclopentylpropyl)phenyl]-                        1738  1.35-1.60(5H, m), 1.70-1.80(4H, m),           butyrate           1.80-1.90(1H, m), 1.96(2H, qn, J=7.5Hz),           pale yellowish brown oil                              2.34(2H, t, J=7.5Hz), 2.65(2H, t,                              J=7.5Hz), 3.67(3H, s), 4.35(1H, t, J=                              7.5Hz), 7.18(2H, d, J=8.5Hz), 7.21(2H,                              d, J=8.5Hz)     218   Methyl 4-[4-[1-Azido-3-(4-                        2100, 0.97(3H, t, J=7.5Hz), 1.49(2H, sex, J=           butoxyphenyl)propyl]-                        1738  7.5Hz), 1.72-1.79(2H, m), 1.96(2H,           phenyl]butyrate    qn, J=7.5Hz), 1.93-2.04(1H, m), 2.06-           pale yellow oil    2.15(1H, m), 2.34(2H, t, J=7.5Hz), 2.54-                              2.67(2H, m), 2.66(2H, t, J=7.5Hz),                              3.66(3H, s), 3.94(2H, t, J=7Hz), 4.35(1H,                              dd, J=8, 6Hz), 6.82(2H, d, J=8.5Hz),                              7.06(2H, d, J=8.5Hz), 7.19(2H,                              d, J=8.5Hz), 7.21(2H, d, J=8.5Hz)     219   Methyl 4-[4-(1-Azido-4-                        2100, 1.55-1.61(1H, m), 1.68-1.90(3H, m),           phenylbutyl)phenyl]-                        1740  1.96(2H, qn, J=7.5Hz), 2.33(2H, t, J=           butyrate           7.5Hz), 2.59-2.67(4H, m), 3.66(3H, s),           pale yellow oil    7.15(1H, t, J=7.5Hz), 7.12-7.20(7H,                              m), 7.24-7.28(2H, m)     220   Methyl 4-[4-(1-Azido-5-                        2100, 1.27-1.38(1H, m), 1.40-1.50(1H, m),           phenylpentyl)phenyl]-                        1738  1.63(2H, qn, J=7.5Hz), 1.70-1.90(2H,           butyrate           m), 1.96(2H, qn, J=7.5Hz), 2.34(2H,           pale yellow oil    t, J=7.5Hz), 2.59(2H, t, J=7.5Hz), 2.65(2H,                              t, J=7.5Hz), 3.67(3H, s), 4.36(1H,                              t, J=7Hz), 7.12-7.21(7H, m), 7.24-                              7.28(2H, m)     221   Methyl 4-[4-(1-Azido-6-                        2100, 1.24-1.46(4H, m), 1.60(2H, qn, J=7.5Hz),           phenylhexyl)phenyl]-                        1738  1.67-1.76(1H, m), 1.77-1.86(1H,           butyrate           m), 1.96(2H, qn, J=7.5Hz), 2.33(2H,           pale yellow oil    t, J=7.5Hz), 2.58(2H, t, J=7.5Hz), 2.65(2H,                              t, J=7.5Hz), 3.66(3H, s), 4.35(1H,                              t, J=7.5Hz), 7.12-7.21(7H, m), 7.24-                              7.29(2H, m)     __________________________________________________________________________

                                      TABLE 45     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     222   Methyl 4-[4-[1-Azido-3-(4-                         2100, 0.92(3H, t, J=7.5Hz), 1.35(2H, sex, J=           butylphenyl)propyl]phenyl]-                         1740  7.5Hz), 1.54-1.62(2H, m), 1.96(2H,           butyrate            qn, J=7.5Hz), 1.98-2.07(1H, m), 2.09-           pale brown oil      2.18(1H, m), 2.34(2H, t, J=7.5Hz), 2.58(2H,                               t, J=7.5Hz), 2.56-2.70(2H, m),                               2.66(2H, t, J=7.5Hz), 3.67(3H, s),                               4.36(1H, dd, J=8.5, 6.5Hz), 7.07(2H,                               d, J=8Hz), 7.10(2H, d, J=8Hz), 7.19(2H,                               d, J=8Hz), 7.22(2H, d, J=8Hz)     223   Methyl 4-[4-[1-Azido-3-(p-                         2100, 1.95-2.06(1H, m), 1.96(2H, qn, J=7.5Hz),           tolyl)propyl]phenyl]-                         1738  2.07-2.17(1H, m), 2.32(3H, s), 2.34(2H,           butyrate            t, J=7.5Hz), 2.55-2.70(2H, m),           pale yellow oil     2.66(2H, t, J=7.5Hz), 3.67(3H, s),                               4.36(1H, dd, J=8, 6Hz), 7.05(2H, d, J=                               8Hz), 7.10(2H, d, J=8Hz), 7.19(2H, d,                               J=8.5Hz), 7.21(2H, d, J=8.5Hz)     224   Methyl 4-(4-[1-Azido-3-(4-                         2100, 1.94-2.04(1H, m), 1.96(2H, qn, J=7.5Hz),           fluorophenyl)propyl]-                         1740  2.07-2.16(1H, m), 2.34(2H, t, J=           phenyl]butyrate     7.5Hz), 2.57-2.72(2H, m), 2.66(2H, t,           colorless oil       J=7.5Hz), 3.67(3H, s), 4.35(1H, dd,                               J=8.5, 6Hz), 6.97(2H, t, J=8.5Hz), 7.11(2H,                               dd, J=8.5, 5.5Hz), 7.20(4H, s)     225   Methyl 4-[4-[1-Azido-3-(3-                         2100, 1.97(2H, qn, J=7.5Hz), 2.00-2.06(1H,           fluorophenyl)propyl]-                         1738  m), 2.09-2.17(1H, m), 2.34(2H, t, J=           phenyl]butyrate     7.5Hz), 2.59-2.74(2H, m), 2.66(2H, t,           pale yellow oil     J=7.5Hz), 3.67(3H, s), 4.37(1H, dd,                               J=8, 6Hz), 6.84-6.96(3H, m), 7.17-7.29(5H, m)     226   Methyl 4-[4-[1-Azido-3-(4-                         2104, 1.96(2H, qn, J=7.5Hz), 1.96-2.04(1H,           chlorophenyl)propyl]-                         1738  m), 2.06-2.18(1H, m), 2.34(2H, t, J=           phenyl]butyrate     7.5Hz), 2.57-2.71(2H, m), 2.66(2H, t,           pale brown oil      J=7.5Hz), 3.67(3H, s), 4.35(1H, dd,                               J=8, 6Hz), 7.09(2H, d, J=8.5Hz), 7.20(4H,                               s), 7.25(2H, d, J=8.5Hz)     __________________________________________________________________________

Reference Example 227 Methyl 4-[4-(1-Amino-2-phenylethyl)phenyl]butyrate

To a solution of 3.10 g of methyl 4-[4-(1-azido-2-phenylethyl)phenyl]butyrate in 30 ml of methanol, 31 mg of platinum oxide was added, and hydrogenation was carried out at an ordinary temperature and under ordinary pressure for 4.5 hours. After the catalyst was filtered off, the filtrate was concentrated under reduced pressure. The residue was added with dilute hydrochloric acid and washed with ether. The aqueous layer was made alkaline with potassium carbonate and then extracted with ether. The ether layer was washed with water and dried, and then the solvent was removed under reduced pressure to yield 2.16 g of brown oil.

IR spectrum ν (liq) cm⁻¹ : 3380, 3300, 1738

NMR spectrum δ (CDCl₃) ppm: 1.73(2H,brs), 1.95(2H,qn,J=7.5 Hz), 2.32(2H,t,J=7.5 Hz), 2.63(2H,t,J=7.5 Hz), 2.83(1H,dd,J=13.5,9 Hz), 3.01(1H,dd,J=13.5,5 Hz), 3.67(3H,s), 4.17(1H,dd,J=9.5 Hz), 7.08-7.17(4H,m), 7.19-7.22(1H,m), 7.26-7.29(4H,m)

The compounds of Reference Examples 228 through 279 shown in Tables 46 to 54 were obtained in the same manner as described in Reference Example 227.

                                      TABLE 46     __________________________________________________________________________     Reference     Example           Compound      I R ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     228   Methyl 3-[4-(1-Amino-2-                         3384, 1.83(2H, brs), 2.62(2H, t, J=8Hz), 2.82(1H,           phenylethyl)phenyl]-                         3300, dd, J=13.5, 9Hz), 2.94(2H, t, J=           propionate    1738  8Hz), 3.00(1H, dd, J=13.5, 5Hz), 3.67(3H,           pale brown oil      s), 4.17(1H, dd, J=9, 5Hz), 7.16(2H,                               d, J=8Hz), 7.20-7.29(7H, m)     229   Methyl 4-[4-[1-Amino-2-(2-                         3384, 1.85(2H, brs), 1.94(2H, qn, J=7.5Hz),           fluorophenyl)ethyl]phenyl]-                         3308, 2.32(2H, t, J=7.5Hz), 2.63(2H, t, J=           butyrate      1738  7.5Hz), 2.88(1H, dd, J=13.5, 8.5Hz),           colorless oil       3.03(1H, dd, J=13.5, 5.5Hz), 3.67(3H,                               s), 4.21(1H, dd, J=8.5, 5.5Hz), 6.99-                               7.22(4H, m), 7.03(2H, d, J=8Hz), 7.13(2H,                               d, J=8Hz), 7.27(2H, d, J=8Hz)     230   Methyl 4-[4-[1-Amino-2-(3-                         3380, 1.48(2H, brs), 1.95(2H, qn, J=7.5Hz),           fluorophenyl)ethyl]phenyl]-                         3310, 2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=           butyrate      1738  7.5Hz), 2.82(1H, dd, J=13.5, 8.5Hz),           colorless oil       2.97(1H, dd, J=13.5, 5Hz), 3.67(3H, s),                               4.16(1H, m), 6.84-6.96(3H, m), 7.14(2H,                               d, J=8Hz), 7.21-7.26(1H, m), 7.25(2H,                               d, J=8Hz)     231   Methyl 4-[4-[1-Amino-2-(4-                         3384, 1.45(2H, brs), 1.95(2H, qn, J=7.5Hz),           fluorophenyl)ethyl]phenyl]-                         3320, 2.33(2H, t, J=7.5Hz), 2.64(2H, t, J=           butyrate      1738  7.5Hz), 2.80(1H, dd, J=13.5, 8.5Hz),           pale brown oil      2.94(1H, dd, J=13.5, 5.5Hz), 3.67(3H,                               s), 4.12(1H, dd, J=8.5, 5.5Hz), 6.95(2H,                               t, J=8.5Hz), 7.09(2H, dd, J=8.5,                               3.5Hz), 7.13(2H, d, J=8Hz), 7.23(2H,                               d, J=8Hz)     232   Methyl 4-[4-[1-Amino-2-(4-                         3384, 1.86(2H, brs), 1.95(2H, qn, J=7.5Hz),           chlorophenyl)ethyl]phenyl]-                         3308, 2.32(2H, t, J=7.5Hz), 2.63(2H, t, J=           butyrate      1738  7.5Hz), 2.83(1H, dd, J=13.5, 8.5Hz),           colorless oil       2.95(1H, dd, J=13.5, 5.5Hz), 3.67(3H,                               s), 4.13(1H, dd, J=8.5, 5.5Hz), 7.05(2H,                               d, J=8.5Hz), 7.13(2H, d, J=8Hz),                               7.23(4H, d, J=8.5Hz)     233   Methyl 4-[4-[1-Amino-2-(p-                         3380, 1.95(2H, qn, J=7.5Hz), 2.32(3H, s), 2.33(2H,           tolyl)ethyl]phenyl]-                         3300, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),           butyrate      1738  2.75(1H, dd, J=14, 9Hz), 2.96(1H,           pale brown oil      dd, J=14, 5Hz), 3.67(3H, s), 4.14(1H,                               dd, J=9, 5Hz), 7.07(2H, , d, J=7.5Hz),                               7.09(2H, d, J=7.5Hz), 7.14(2H, d, J=                               7.5Hz), 7.28(2H, d, J=7.5Hz)     __________________________________________________________________________

                                      TABLE 47     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     234   Methyl 4-[4-(1-Aminoethyl)-                         3376, 1.39(3H, d, J=6.5Hz), 1.90-1.99(2H,           phenyl]butyrate                         3312, br), 1.95(2H, qn, J=7.5Hz), 2.33(2H,           pale brown oil                         1738  t, J=7.5Hz), 2.63(2H, t, J=7.5Hz), 3.66                               (3H, s), 4.10(1H, q, J=6.5Hz), 7.14                               (2H, d, J=8Hz), 7.27(2H, d, J=8Hz)     235   Methyl 4-[4-(1-Amino-                         3384, 0.86(3H, t, J=7.5Hz), 1.70(2H, m), 1.92           propyl)phenyl]butyrate                         1738  (2H, brs), 1.95(2H, qn, J=7.5Hz), 2.33           colorless oil       (2H, t, J=7.5Hz), 2.63(2H, t, J=7.5Hz),                               3.66(3H, s), 3.79(1H, t, J=7Hz),                               7.13(2H, d, J=8Hz), 7.23(2H, d, J=8Hz     236   Methyl 5-[4-(1-Amino-2-                         3384, 1.60-1.70(4H, m), 1.91(2H, brs), 2.3           phenylethyl)phenyl]-                         3310, 3(2H, t, J=7.5Hz), 2.61(2H, t, J=7.5Hz),           valerate      1738  2.83(1H, dd, J=13.5, 8.5Hz), 3.01           pale brown oil      (1H, dd, J=13.5, 5Hz), 3.66(3H, s), 4.17                               (1H, dd, J=8.5, 5Hz), 7.13(2H, d, J=                               8.5Hz), 7.16-7.29(7H, m)     237   Methyl 4-[4-(1-Aminobutyl)-                         3376, 0.90(3H, t, J=7.5Hz), 1.17-1.29(1H,           phenyl]butyrate                         3300, m), 1.30-1.56(3H, m), 1.56-1.70(2H,           pale yellow oil                         1738  m), 1.95(2H, qn, J=7.5Hz), 2.33(2H, t,                               J=7.5Hz), 2.63(2H, t, J=7.5Hz), 3.6                               6(3H, s), 3.86(1H, t, J=7Hz), 7.13(2H,                               d, J=8.5Hz), 7.22(2H, d, J=8.5Hz)     238   Methyl 4-[4-(1-Amino-                         3384, 0.87(3H, t, J=7Hz), 1.12-1.24(1H, m),           pentyl)phenyl]butyrate                         3300, 1.24-1.37(3H, m), 1.51(2H, brs), 1.57-           colorless oil 1738  1.72(2H, m), 1.95(2H, qn, J=7.5Hz),                               2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                               7.5Hz), 3.67(3H, s), 3.84(1H, t, J=7Hz),                               7.13(2H, d, J=8Hz), 7.22(2H, d, J=                               8Hz)     239   Methyl 4-[4-(1-Aminohexyl)-                         3384, 0.86(3H, t, J=7Hz), 1.15-1.39(6H, m),           phenyl]butyrate                         3305, 1.50(2H, brs), 1.56-1.70(2H, m), l.95           colorless oil 1738  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.63(2H, t, J=7.5Hz), 3.66(3H,                               s), 3.84(1H, t, J=7Hz), 7.13(2H, d, J=                               8Hz), 7.22(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 48     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     240   Methyl 4-[4-(1-Aminodecyl)-                         3384, 0.87(3H, t, J=7Hz), 1.16-1.34(14H, m,           phenyl)butyrate                         3320, 1.49(2H, brs), 1.60-1.66(2H, m), l.95           colorless oil 1742  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.63(2H, t, J=7.5Hz), 3.67(3H, s),                               3.83(1H, t, J=7Hz), 7.13(2H, d, J=                               8Hz), 7.22(2H, d, J=8Hz)     241   Methyl 4-[4-(1-Amino-2-                         3384, 0.77(3H, d, J=7Hz), 0.98(3H, d, J=7Hz),           methylpropyl)phenyl]-                         3320, 1.87(1H, m), 1.95(2H, qn, J=7.5Hz),           butyrate      1738  1.80-2.20(2H, brs), 2.33(2H, t, J=7.5Hz),           colorless oil       2.63(2H, t, J=7.5Hz), 3.60(1H,                               d, J=7Hz), 3.67(3H, s), 7.12(2H, d, J=                               8Hz), 7.20(2H, d, J=8Hz)     242   Methyl 4-[4-(1-Amino-3-                         3380, 0.90(3H, d, J=6Hz), 0.92(3H, d, J=6Hz),           methylbutyl)phenyl]-                         3315, 1.46-1.59(3H, m), 1.51(2H, s), 1.9           butyrate      1738  5(2H, qn, J=7.5Hz), 2.34(2H, t, J=7.5Hz),           colorless oil       2.63(2H, t, J=7.5Hz), 3.66(3H, s),                               3.92(1H, t, J=7Hz), 7.13(2H, d, J=8Hz),                               7.22(2H, d, J=8Hz)     243   Methyl 4-[4-(1-Amino-4-                         3384, 0.85(3H, d, J=7Hz), 0.86(3H, d, J=7Hz),           methylpentyl)phenyl]-                         3315, 1.04-1.11(1H, m), 1.20-1.27(1H, m           butyrate      1738  1.48-1.56(1H, m), 1.54(2H, s), 1.60-           colorless oil       1.68(2H, m), 1.95(2H, qn, J=7.5Hz),                               2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                               7.5Hz), 3.67(3H, s), 3.81(1H, t, J=7Hz),                               7.13(2H, d, J=8Hz), 7.22(2H, d, J=                               8Hz)     244   Methyl 4-(4-(1-Amino-3, 3-                         3384, 0.90(9H, s), 1.25(2H, brs), 1.60(1H,           dimethylbutyl)phenyl]-                         3320, dd, J=14, 6Hz), 1.69(IH, dd, J=14, 6Hz),           butyrate      1738  1.94(2H, qn, J=7.5Hz), 2.32(2H, t,           colorless oil       J=7.5Hz), 2.63(2H, t, J=7.5Hz), 3.67                               (3H, s), 3.99(1H, t, J=6Hz), 7.12(2H,                               d, J=8Hz), 7.23(2H, d, J=8Hz)     245   Methyl 4-[4-(Aminocyclo-                         3384, 1.03-1.11(1H, m), 1.30-1.40(2H, m),           pentylmethyl)phenyl]-                         3320, 1.40-1.50(1H, m), 1.50-1.61(2H, m),           butyrate      1738  1.61-1.71(1H, m), 1.90-1.96(1H, m),           pale brown oil      1.95(2H, qn, J=7.5Hz), 2.07(1H, m), 2.33                               (2H, t, J=7.5Hz), 2.63(2H, t, J=7.5Hz),                               3.60(1H, d, J=9Hz), 3.66(3H, s),                               7.12(2H, d, J=8.5Hz), 7.23(2H, d, J=                               8.5Hz)     __________________________________________________________________________

                                      TABLE 49     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     246   Methyl 4-[4-(Aminocyclo-                        3384, 0.80-0.90(1H, m), 0.94-1.28(4H, m),           hexylmethyl)phenyl]-                        3320, 1.33-1.43(1H, m), 1.45-1.55(1H, m),           butyrate     1738  1.55-1.68(2H, m), 1.68-1.80(1H, m),           pale yellow oil    1.92-1.98(1H, m), 1.95(2H, qn, J=7.5Hz),                              2.10(2H, brs), 2.33(2H, t, J=7.5Hz),                              2.63(2H, t, J=7.5Hz), 3.59(1H, d,                              J=8Hz), 3.67(3H, s), 7.12(2H, d, J=8Hz),                              7.18(2H, d, J=8Hz)     247   Methyl 4-[4-(Aminocyclo-                        3388, 1.10-1.21(1H, m), 1.24-1.76(13H, m),           heptylmethyl)phenyl]-                        3320, 1.78-1.88(1H, m), 1.95(2H, qn, J=7.5Hz),           butyrate     1738  2.33(2H, t, J=7.5Hz), 2.63(2H,           pale brown oil     t, J=7.5Hz), 3.67(3H, s), 3.71(1H, d,                              J=7Hz), 7.12(2H, d, J=8Hz), 7.20(2H,                              d, J=8Hz)     248   Methyl 4-[4-(1-Amino-2-                        3383, 1.02-1.18(2H, m), 1.42-1.52(2H, m),           cyclopentylethyl)phenyl]-                        3315, 1.50(2H, s), 1.53-1.62(2H, m), 1.63-           butyrate     1738  1.72(4H, m), 1.73-1.82(1H, m), 1.95           colorless oil      (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                              2.63(2H, t, J=7.5Hz), 3.67(3H, s),                              3.87(1H, t, J=7Hz), 7.13(2H, d, J=8Hz),                              7.22(2H, d, J=8Hz)     249   Methyl 4-[4-(1-Amino-2-                        3384, 0.87-0.96(2H, m), 1.10-1.30(4H, m),           cyclohexylethyl)phenyl]-                        3315, 1.46(2H, brs), 1.47-1.58(2H, m), 1.6           butyrate     1738  1-1.75(5H, m), 1.95(2H, qn, J=7.5Hz),           colorless oil      2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                              7.5Hz), 3.67(3H, s), 3.96(1H, t, J=7.5Hz),                              7.13(2H, d, J=8Hz), 7.21(2H, d,                              J=8Hz)     250   Methyl 4-[4-(1-Amino-3-                        3372, 0.78-0.90(2H, m), 1.02-1.29(6H, m),           cyclohexylpropyl)phenyl]-                        3320, 1.50(2H, brs), 1.57-1.71(7H, m), 1.95           butyrate     1740  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),           pale brown oil     2.63(2H, t, J=7.5Hz), 3.67(3H, s),                              3.80(1H, t, J=7Hz), 7.13(2H, d, J=8Hz),                              7.21(2H, d, J=8Hz)     251   Methyl 4-[4-(1-Amino-4-                        3384, 0.78-0.88(2H, m), 1.07-1.23(7H, m),           cyclohexylbutyl)phenyl]-                        3310, 1.28-1.39(1H, m), 1.55-1.70(7H, m),           butyrate     1740  1.57(2H, brs), 1.95(2H, qn, J=7.5Hz),           pale brown oil     2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                              7.5Hz), 3.67(3H, s), 3.84(1H, t, J=7Hz),                              7.13(2H, d, J=8Hz), 7.22(2H, d, J=                              8Hz)     __________________________________________________________________________

                                      TABLE 50     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     252   Methyl 4-[4-(1-Amino-5-                         3384, 0.78-0.87(2H, m), 1.08-1.21(6H, m),           cyclohexylpentyl)phenyl]-                         3325, 1.22-1.39(4H, m), 1.59-1.68(7H, m),           butyrate      1740  1.63(2H, brs), 1.95(2H, qn, J=7.5Hz),           pale brown oil      2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                               7.5Hz), 3.66(3H, s), 3.84(1H, t, J=7Hz),                               7.13(2H, d, J=8Hz), 7.22(2H, d, J=                               8Hz)     253   Methyl 4-[4-(1-Amino-6-                         3384, 0.77-0.90(2H, m), 1.05-1.40(12H, m),           cyclohexylhexyl)phenyl]-                         1740  1.47(2H, brs), 1.58-1.72(7H, m), 1.95           butyrate            (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),           colorless oil       2.63(2H, t, J=7.5Hz), 3.66(3H,                               s), 3.83(1H, t, J=7Hz), 7.13(2H, d, J=                               8Hz), 7.21(2H, d, J=8Hz)     254   Methyl trans-4-[4-                         3384, 0.76-1.05(4H, m), 0.84(3H, d, J=6.5Hz),           [Amino(4-methylcyclohexyl)-                         3310, 1.20-1.64(6H, m), 1.70-1.76(1H,           methyl]phenyl]butyrate                         1738  m), 1.90-1.99(3H, m), 2.33(2H, t, J=7.5Hz),           pale yellow viscous oil                               2.63(2H, t, J=7.5Hz), 3.55(1H,                               d, J=7.5Hz), 3.67(3H, s), 7.12(2H, d,                               J=8Hz), 7.18(2H, d, J=8Hz)     255   Methyl trans-4-[4-                         3388, 0.72-1.54(17H, m), 0.86(3H, t, J=7Hz),           [Amino(4-pentylcyclohexyl)-                         3320, 1.62-1.70(1H, m), 1.74-1.84(1H, m),           methyl]phenyl]butyrate                         1742  1.93-2.00(1H, m), 1.95(2H, qn, J=7.5Hz),           colorless viscous oil                               2.33(2H, t, J=7.5Hz), 2.63(2H,           Hydrochloride       t, J=7.5Hz), 3.55(1H, d, J=7.5Hz), 3.67           colorless needles (AcOEt)                               (3H, s), 7.11(2H, d, J=8Hz), 7.18           mp 212˜212.5° C.                               (2H, d, J=8Hz)     256   Methyl 4-[4-[2-(1-                         3384, 1.44-1.69(15H, m), 1.92-1.97(4H, m),           Adamantyl)-1-aminoethyl]-                         3320, 2.31(2H, t, J=7.5Hz), 2.61(2H, t, J=           phenyl]butyrate                         1740  7.5Hz), 3.69(3H, s), 4.04(1H, t, J=6Hz),           colorless oil       7.11(2H, d, J=8Hz), 7.22(2H, d, J=                               8Hz)     257   Methyl 4-[4-[1-Amino-2-(2-                         3384, 1.01-1.12(4H, m), 1.26-1.71(7H, m),           norbornyl)ethyl]phenyl]-                         3320, 2.16-2.19(2H, m), 1.95(2H, qn, J=7.5Hz),           butyrate      1738  2.33(2H, t, J=7.5Hz), 2.63(2H, t,           pale brown oil      J=7.5Hz), 3.67(3H, s), 3.84-3.89(lH,                               m), 7.13(2H, d, J=8Hz), 7.22(2H, d,                               J=8Hz)     __________________________________________________________________________

                                      TABLE 51     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     258   Methyl 4-[4-(1-Amino-3-                         3380, 1.66(2H, brs), 1.93-2.05(2H, m), 1.96           phenylpropyl)phenyl]-                         3300, (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),           butyrate      1738  2.53-2.69(2H, m), 2.64(2H, t, J=           colorless oil       7.5Hz), 3.67(3H, s), 3.88(1H, t, J=6.5Hz),                               7.13-7.19(5H, m), 7.22-7.28(4H, m)     259   Methyl 5-[4-(1-Amino-                         3384, 0.87(3H, t, J=7Hz), 1.13-1.24(1H, m),           pentyl)phenyl]valerate                         3330, 1.25-1.36(3H, m), 1.61(2H, brs)1.60-           colorless oil 1738  1.73(6H, m), 2.33(2H, t, J=7.5Hz)                               2.61(2H, t, J=7.5Hz), 3.66(3H, s), 3.83                               (1H, t, J=6.5Hz), 7.13(2H, d, J=8Hz),                               7.21(2H, d, J=8Hz)     260   Methyl 5-[4-(1-Aminohexyl)-                         3384, 0.86(3H, t, J=7Hz), 1.15-1.38(6H, m)           phenyl]valerate                         3320, 1.57(2H, brs), 1.58-1.70(6H, m), 2.33           colorless oil 1738  (2H, t, J=7Hz), 2.61(2H, t, J=7.5Hz),                               3.66(3H, s), 3.83(1H, t, J=7Hz), 7.12                               (2H, d, J=8Hz), 7.21(2H, d, J=Hz)     261   Methyl 5-[4-(1-Amino-2-                         3384, 0.85-0.99(2H, m), 1.08-1.32(4H, m),           cyclohexylethyl)phenyl]-                         3310, 1.42-1.80(13H, m), 2.33(2H, t, J=7Hz),           valerate      1738  2.61(2H, t, J=7.5Hz), 3.66(3H, s),           colorless oil       3.96(1H, t, J=7.5Hz), 7.12(2H, d, J=8                               Hz), 7.20(2H, d, J=8Hz)     262   Methyl 4-[4-(1-Amino-                         3380, 0.86(3H, t, J=7Hz), 1.16-1.37(8H, m)           heptyl)phenyl]butyrate                         3304, 1.55(2H, brs), 1.57-1.70(2H, m), 1.95           pale brown oil                         1738  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.63(2H, t, J=7.5Hz), 3.67(3H,                               s), 3.83(1H, t, J=7Hz), 7.13(2H, d, J=                               8Hz), 7.21(2H, d, J=8Hz)     263   Methyl 4-(4-(1-Aminooctyl)-                         3380, 0.86(3H, t, J=7Hz), 1.14-1.37(10H, m),           phenyl]butyrate                         3320, 1.52(2H, brs), 1.58-1.69(2H, m), 1.95           pale brown oil                         1738  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7,5Hz),                               2.63(2H, t, J=7.5Hz), 3.67(3H,                               S), 3.84(1H, t, J=7Hz), 7.13(2H, d, J=                               8Hz), 7.22(2H, d, J=8Hz)     264   Methyl 4-[4-(1-Aminononyl)-                         3390, 0.87(3H, t, J=7Hz), 1.14-1.37(12H, m),           phenyl]butyrate                         3320, 1.57-1.71(2H, m), 1.65(2H, brs), 1.95           pale yellow oil                         1740  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz),                               2.63(2H, t, J, 7.5Hz), 3.67(3H                               S), 3.84(1H, t, J=7Hz), 7.13(2H, d, J=                               Hz), 7.22(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 52     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     265   Methyl 4-[4-(1-Amino-5-                        3376, 0.83(3H, d, J=7Hz), 0.84(3H, d, J=7Hz),           methylhexyl)phenyl]-                        3310, 1.13-1.23(3H, m), 1.28-1.38(1H, m),           butyrate     1738  1.45-1.55(1H, m), 1.57-1.66(2H, m),           pale brown oil     1.61(2H, brs), 1.95(2H, qn, J=7.5Hz),                              2.33(2H, t, J=7.5Hz), 2.63(2H, t,                              J=7.5Hz), 3.66(3H, s), 3.84(1H, t, J=                              7Hz), 7.13(2H, d, J=8Hz), 7.22(2H, d,                              J=8Hz)     266   Methyl 4-[4-(1-Amino-6-                        3384, 0.84(6H, d, J=6Hz), 1.09-1.36(6H, m),           methylheptyl)phenyl]-                        3320, 1.44-1.55(IH, m), 1.59(2H, brs),l.60-           butyrate     1740  1.66(2H, m), 1.95(2H, qn, J=7.5Hz),           pale brown oil     2.33(2H, t, J=7.5Hz), 2.63(2H, t, J=                              7.5Hz), 3.67(3H, s), 3.84(1H, t, J=7Hz),                              7.13(2H, d, J=8Hz), 7.22(2H, d, J=8Hz)     267   Methyl 4-(4-(1-Amino-4,4-                        3384, 0.85(9H, s), 0.99-1.08(1H, m), 1.23-           dimethylpentyl)phenyl]-                        3320, 1.32(1H, m), 1.52(2H, brs), 1.57-1.64           butyrate     1738  (2H, m), 1.96(2H, qn, J=7.5Hz), 2.33           pale brown oil     (2H, t, J=7.5Hz), 2.64(2H, t, J=7.5Hz),                              3.67(3H, s), 3.77(1H, t, J=7Hz), 7.14                              (2H, d, J=8Hz), 7.22(2H, d, J=8Hz)     268   Methyl 4-(4-(1-Amino-5,5-                        3384, 0.84(9H, s), 1.12-1.24(3H, m), 1.24-           dimethylhexyl)phenyl]-                        3330, 1.37(1H, m), 1.58-1.67(2H, m), 1.60           butyrate     1738  (2H, brs), 1.95(2H, qn, J=7.5Hz), 2.33           pale brown oil     (2H, t, J=7.5Hz), 2.63(2H, t, J=7.5Hz),                              3.66(3H, s), 3.86(1H, t, J=7Hz), 7.13                              (2H, d, J=8Hz), 7.22(2H, d, J=8Hz)     269   Methyl 4-[4-(1-Amino-6,6-                        3380, 0.84(9H, s), 1.10-1.35(6H, m), 1.61           dimethylheptyl)phenyl1-                        3320, (2H, brs), 1.60-1.71(2H, m), 1.95(2H,           butyrate     1740  qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz), 2.63           pale brown oil     (2H, t, J=7.5Hz), 3.67(3H, s), 3.84                              (1H, t, J=7Hz), 7.13(2H, d, J=8.5Hz),                              7.22(2H, d, J=8.5Hz)     270   Methyl 4-[4-(-Amino-3-                        3384, 1.00-1.10(2H, m), 1.15-1.25(1H, m),           cyclopentyl)phenyl]-                        1738  1.30-1.40(1H, m), 1.40-1.80(11H, m),           butyrate           1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           pale yellowish brown oil                              7.5Hz), 2.63(2H, t, J=7.5Hz), 3.67                              (3H, s), 3.82(1H, t, J=7.5Hz), 7.13(2H,                              d, J=Hz), 7.22(2H, , d, J=8Hz)     __________________________________________________________________________

                                      TABLE 53     __________________________________________________________________________     Reference     Example           Compound      IR ν                               NMR     No.   Appearance    (liq) cm.sup.-1                               δ (CDCl.sub.3)     __________________________________________________________________________     271   Methyl 4-[4-[1-Amino-3-(4-                         3390, 0.97(3H, t, J=7.5Hz), 1.48(2H, sex, J=           butoxyphenyl)propyl]-                         3330, 7.5Hz), 1.54(2H, brs), 1.71-1.78(2H,           phenyl]butyrate                         1738  m), 1.90-2.00(2H, m), 1.95(2H, qn,           pale brown oil      J=7.5Hz), 2.33(2H, t, J=7.5Hz), 2.45-                               2.61(2H, m), 2.64(2H, t, J=7.5Hz), 3.67                               (3H, s), 3.86(1H, t, J=7Hz), 3.93                               (2H, t, J=7Hz), 6.80(2H, d, J=8.5Hz), 7.05                               (2H, d, J=8.5Hz), 7.14(2H, d, J=8.5Hz),                               5Hz), 7.23(2H, d, J=8.5Hz)     272   Methyl 4-[4-(1-Amino-4-                         3380, 1.44-1.74(6H, m), 1.95(2H, qn, J=7.5Hz),           phenylbutyl)phenyl]-                         3300, 2.33(2H, t, J=7.5Hz), 2.57-2.65           butyrate      1738  (4H, m), 3.66(3H, s), 3.86(1H, t, J=7Hz),           pale yellow oil     7.10-7.27(9H, m)     273   Methyl 4-[4-(1-Amino-5-                         3384, 1.20-1.31(1H, m), 1.34-1.72(7H, m),           phenylpentyl)phenyl]-                         3320, 1.95(2H, qn, J=7.5Hz), 2.33(2H, t, J=           butyrate      1738  7.5Hz), 2.57(2H, t, J=7.5Hz), 2.63(2           pale yellow oil     H, t, J=7.5Hz), 3.67(3H, s), 3.84(1H,                               t, J=7.5Hz), 7.11-7.28(9H, m)     274   Methyl 4-[4-(1-Amino-6-                         3380, 1.18-1.68(10H, m), 1.95(2H, qn, J=7.           phenylhexyl)phenyl]-                         3320, 5Hz), 2.33(2H, t, J=7.5Hz), 2.57(2H,           butyrate      1738  t, J=7.5Hz), 2.63(2H, t, J=7.5Hz), 3.66           colorless oil       (3H, s), 3.82(1H, t, J=7.5Hz), 7.11-                               7.18(3H, m), 7.13(2H, d, J=8Hz), 7.20                               (2H, d, J=8Hz), 7.23-7.28(2H, m)     275   Methyl 4-[4-(1-Amino-3-(4-                         3380, 0.91(3H, t, J=7.5Hz), 1.34(2H, sex,           butylphenyl)propyl]phenyl]-                         3310, J=7.5Hz), 1.50-1.61(2H, m), 1.53(2H           butyrate      1738  brs), 1.92-2.01(4H, m), 2.33(2H, t,           pale brown oil      J=7.5Hz), 2.49-2.64(2H, m), 2.56(2H                               t, J=8Hz), 2.64(2H, t, J=7.5Hz), 3.66                               (3H, s), 3.87(1H, t, J=7Hz), 7.06-7.10                               (4H, m), 7.14(2H, d, J=8Hz), 7.23(2                               H, d, J=8Hz)     276   Methyl 4-[4-(1-Amino-3-(p-                         3384, 1.53(2H, brs), 1.90-2.00(2H, m), 1.96           tolyl)propyl]phenyl]-                         3320, (2H, qn, J=7.5Hz), 2.31(3H, s), 2.33           butyrate      1738  (2H, t, J=7.5Hz), 2.47-2.65(2H, m), 2.64           pale brown oil      (2H, t, J=7.5Hz), 3.67(3H, s), 3.87                               (1H, t, J=7Hz), 7.04(2H, d, J=8Hz), 7.07                               (2H, d, J=8Hz), 7.14(2H, d, J=8Hz),                               7.23(2H, d, J=8Hz)     __________________________________________________________________________

                                      TABLE 54     __________________________________________________________________________     Reference     Example           Compound     IR ν                              NMR     No.   Appearance   (liq) cm.sup.-1                              δ (CDCl.sub.3)     __________________________________________________________________________     277   Methyl 4-[4-[1-Amino-3-(4-                        3384, 1.60(2H, brs), 1.90-2.02(2H, m), 1.96           fluorophenyl)propyl]-                        3300, (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz,           phenyl]butyrate                        1738  2.49-2.66(2H, m), 2.64(2H, t, J=           colorless oil      7.5Hz), 3.67(3H, s), 3.86(1H, t, J=7Hz,                              6.94(2H, t, J=8.5Hz), 7.09(2H, dd,                              J=8.5, 5.5Hz), 7.15(2H, d, J=8Hz), 7.22                              (2H, d, J=8Hz)     278   Methyl 4-[4-[1-Amino-3-(3-                        3384, 1.55(2H, brs), 1.92-2.01(4H, m), 2.34           fluorophenyl)propyl]-                        3320, (2H, t, J=7.5Hz), 2.52-2.63(2H, m),           phenyl]butyrate                        1738  2.64(2H, t, J=7.5Hz), 3.67(3H, s), 3.87           pale yellow oil    (1H, t, J=7.5Hz), 6.83-6.96(3H, m),                              7.15(2H, d, J=8Hz), 7.18-7.24(1H, m),                              7.23(2H, d, J=8Hz)     279   Methyl 4-[4-[1-Amino-3-(4-                        3380  1.55(2H, brs), 1.88-2.03(2H, m), 1.96           chlorophenyl)propyl]-                        3316  (2H, qn, J=7.5Hz), 2.33(2H, t, J=7.5Hz,           phenyl]butyrate                        1738  2.48-2.63(2H, m), 2.64(2H, t, J=           pale brown oil     7.5Hz), 3.67(3H, s), 3.85(1H, t, J=7Hz),                              7.07(2H, d, J=8.5Hz), 7.22(2H, d,                              J=8Hz), 7.22(2H, d, J=8.5Hz)     __________________________________________________________________________

Example 1 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

To a solution of 2.16 g of methyl 4-[4-(1-amino-2-phenylethyl)phenyl]butyrate and 1.11 ml of triethylamine in 10 ml of methylene chloride, a solution of 1.53 g of 4-chlorobenzenesulfonyl chloride in 10 ml of methylene chloride was added dropwise under ice-cooling.

The reaction mixture was stirred at room temperature for 1.5 hours, and then washed with dilute hydrochloric acid and water successively. The methylene chloride layer was dried and then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride→methylene chloride:ethyl acetate=5:1) to yield 2.44 g of colorless crystals. Recrystallization from a mixture of isopropyl ether and ethyl acetate gave colorless prisms, mp 93.5°˜94° C.

Analysis for C₂₅ H₂₆ ClNO₄ S

Calculated C, 63.62; H, 5.55; N, 2.97 Found C, 63.58; H, 5.60; N, 2.94

The compounds of Examples 2 through 61 were prepared in the same manner as described in Example 1.

Example 2 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)ethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 92°˜93° C.

Analysis for C₁₉ H₂₂ ClNO₄ S

Calculated C, 57.64; H, 5.60; N, 3.54 Found C, 57.79; H, 5.57; N, 3.46

Example 3 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)propyl]phenyl]butyrate

Appearance colorless columns (i-Pr₂ O)

mp 76° C.

Analysis for C₂₀ H₂₄ ClNO₄ S

Calculated C, 58.60; H, 5.90; N, 3.42 Found C, 58.54; H, 5.83; N, 3.42

Example 4 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)butyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 66.5°˜67.5° C.

Analysis for C₂₁ H₂₆ ClNO₄ S

Calculated C, 59.49; H, 6.18; N, 3.30 Found C, 59.50; H, 6.45; N, 3.44

Example 5 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)pentyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 65°˜66.5° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.12; H, 6.65; N, 3.18

Example 6 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 79°˜80° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 60.92; H, 6.94; N, 3.05

Example 7 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)decyl]phenyl]butyrate

Appearance colorless plates (i-Pr₂ O)

mp 68.5°˜69° C.

Analysis for C₂₇ H₃₈ ClNO₄ S

Calculated C, 63.82; H, 7.54; N, 2.76 Found C, 63.54; H, 7.76; N, 2.78

Example 8 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 96°˜96.5° C.

Analysis for C₂₁ H₂₆ ClNO₄ S

Calculated C, 59.49; H, 6.18; N, 3.30 Found C, 59.57; H, 6.25; N, 3.41

Example 9 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-methylbutyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O--AcOEt)

mp 82°˜83° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.28; H, 6.64; N, 3.22

Example 10 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-4-methylpentyl]phenyl]butyrate

Appearance colorless plates (i-Pr₂ O--AcOEt)

mp 89°˜90.5° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 61.04; H, 6.85; N, 3.06

Example 11 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3,3-dimethylbutyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 62.5°˜64° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 60.94; H, 6.84; N, 3.01

Example 12 Methyl 4-[4-[(4-Chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 84° C.

Analysis for C₂₃ H₂₈ ClNO₄ S

Calculated C, 61.39; H, 6.27; N, 3.11 Found C, 61.30; H, 6.19; N, 3.11

Example 13 Methyl 4-[4-[(4-Chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyrate

Appearance colorless needles (i-PrOH)

mp 97.5°˜98° C.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 61.90; H, 6.47; N, 3.00

Example 14 Methyl 4-[4-[(4-Chlorophenylsulfonylamino)cycloheptylmethyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 102°˜103.5° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.68; H, 6.93; N, 2.88

Example 15 Methyl trans-4-[4-[(4-Chlorophenylsulfonylamino)(4-methylcyclohexyl)methyl]phenyl]butyrate

Appearance colorless needles (EtOH)

mp 132°˜133° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.54; H, 7.02; N, 3.11

Example 16 Methyl trans-4-[4-[(4-Chlorophenylsulfonylamino)(4-pentylcyclohexyl)methyl]phenyl]butyrate

Appearance colorless needles (EtOH)

mp 115°˜116° C.

Analysis for C₂₉ H₄₀ ClNO₄ S

Calculated C, 65.21; H, 7.55; N, 2.62 Found C, 64.96; H, 7.81; N, 2.71

Example 17 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclopentylethyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O--AcOEt)

mp 102.5°˜104° C.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 62.04; H, 6.70; N, 3.02

Example 18 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O--AcOEt)

mp 115°˜116° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.56; H, 6.92; N, 2.89

Example 19 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-cyclohexylpropyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-P₂ O)

mp 104°˜105° C.

Analysis for C₂₆ H₃₄ ClNO₄ S

Calculated C, 63.46; H, 6.96; N, 2.85 Found C, 63.46; H, 7.21; N, 2.82

Example 20 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-4-cyclohexylbutyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 81°˜82° C.

Analysis for C₂₇ H₃₆ ClNO₄ S

Calculated C, 64.08; H, 7.17; N, 2.77 Found C, 64.11; H, 7.43; N, 2.72

Example 21 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-cyclohexylpentyl]phenyl]butyrate

Appearance colorless plates (i-Pr₂ O)

mp 87.5°˜89.5° C.

Analysis for C₂₈ H₃₈ ClNO₄ S

Calculated C, 64.66; H, 7.36; N, 2.69 Found C, 64.42; H, 7.64; N, 2.68

Example 22 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-cyclohexylhexyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 82°˜83.5° C.

Analysis for C₂₉ H₄₀ ClNO₄ S

Calculated C, 65.21; H, 7.55; N, 2.62 Found C, 65.10; H, 7.75; N, 2.57

Example 23 Methyl 4-[4-[2-(1-Adamantyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 127.5°˜128° C.

Analysis for C₂₉ H₃₆ ClNO₄ S

Calculated C, 65.70; H, 6.84; N, 2.64 Found C, 65.54; H, 7.01; N, 2.68

Example 24 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(2-norbornyl)ethyl]phenyl]butyrate

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 112.5°˜113.5° C.

Analysis for C₂₆ H₃₃ ClNO₄ S

Calculated C, 63.59; H, 6.77; N, 2.85 Found C, 63.52; H, 6.63; N, 2.76

Example 25 Methyl 3-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]propionate

Appearance colorless plates (AcOEt-i-Pr₂ O)

mp 114°˜115° C.

Analysis for C₂₄ H₂₄ ClNO₄ S

Calculated C, 62.94; H, 5.28; N, 3.06 Found C, 63.02; H, 5.50; N, 3.01

Example 26 Methyl 4-[4-[2-Phenyl-1-(phenylsulfonylamino)ethyl]phenyl]butyrate

Appearance colorless plates (AcOEt-i-Pr₂ O)

mp 93°˜94.5° C.

Analysis for C₂₅ H₂₇ NO₄ S

Calculated C, 68.62; H, 6.22; N, 3.20 Found C, 68.42; H, 6.08; N, 3.16

Example 27 Methyl 4-[4-[1-(4-Fluorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 108.5°˜110° C.

Analysis for C₂₅ H₂₆ FNO₄ S

Calculated C, 65.91; H, 5.75; N, 3.07 Found C, 65.71; H, 5.80; N, 3.01

Example 28 Methyl 4-[4-[1-(4-Bromophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 101°˜102° C.

Analysis for C₂₅ H₂₆ BrNO₄ S

Calculated C, 58.14; H, 5.07; N, 2.71 Found C, 58.09; H, 5.04; N, 2.95

Example 29 Methyl 4-[4-[1-(p-Tolylsulfonylamino)-2-phenylethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 103.5°˜104.5° C.

Analysis for C₂₆ H₂₉ NO₄ S

Calculated C, 69.15; H, 6.47; N, 3.10 Found C, 69.14; H, 6.56; N, 3.03

Example 30 Methyl 4-[4-[1-(4-Methoxysulfonylamino)-2-phenylethyl]phenyl]butyrate

Appearance colorless columns (AcOEt-i-Pr₂ O)

mp 114.5°˜115.5° C.

Analysis for C₂₆ H₂₉ NO₅ S

Calculated C, 66.79; H, 6.25; N, 3.00 Found C, 66.74; H, 6.28; N, 2.95

Example 31 Methyl 5-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]valerate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 107.5°˜109° C.

Analysis for C₂₆ H₂₈ ClNO₄ S

Calculated C, 64.25; H, 5.81; N, 2.88 Found C, 64.25; H, 6.05; N, 2.79

Example 32 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(2-fluorophenyl)ethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 97°˜98° C.

Analysis for C₂₅ H₂₅ ClFNO₄ S

Calculated C, 61.28; H, 5.14; N, 2.86 Found C, 61.25; H, 5.11; N, 2.90

Example 33 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 88°˜90° C.

Analysis for C₂₅ H₂₅ ClFNO₄ S

Calculated C, 61.28; H, 5.14; N, 2.86 Found C, 61.15; H, 5.08; N, 2.83

Example 34 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyrate

Appearance pale brown prisms (AcOEt-i-Pr₂ O)

mp 104.5°˜106° C.

Analysis for C₂₅ H₂₅ ClFNO₄ S

Calculated C, 61.28; H, 5.14; N, 2.86 Found C, 61.24; H, 5.10; N, 2.92

Example 35 Methyl 4-[4-[2-(4-Chlorophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyrate

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 108°˜109.5° C.

Analysis for C₂₅ H₂₅ Cl₂ NO₄ S

Calculated C, 59.29; H, 4.98; N, 2.77 Found C, 59.33; H, 4.98; N, 2.80

Example 36 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyrate

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 109.5°˜110.5° C.

Analysis for C₂₆ H₂₈ ClNO₄ S

Calculated C, 64.25; H, 5.81; N, 2.88 Found C, 64.05; H, 5.89; N, 2.90

Example 37 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyrate

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 112°˜114° C.

Analysis for C₂₆ H₂₈ ClNO₄ S

Calculated C, 64.25; H, 5.81; N, 2.88 Found C, 64.19; H, 5.95; N, 2.89

Example 38 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)heptyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 86°˜88° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.69; H, 7.13; N, 3.20

Example 39 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)octyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 72°˜74.5° C.

Analysis for C₂₅ H₃₄ ClNO₄ S

Calculated C, 62.55; H, 7.14; N, 2.92 Found C, 62.59; H, 7.39; N, 3.11

Example 40 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)nonyl]phenyl]butyrate

Appearance colorless flakes (i-Pr₂ O)

mp 81°˜83° C.

Analysis for C₂₆ H₂₆ ClNO₄ S

Calculated C, 63.20; H, 7.34; N, 2.83 Found C, 63.20; H, 7.38; N, 2.82

Example 41 Methyl 5-[4-[1-(4-Chlorophenylsulfonylamino)pentyl]phenyl]valerate

Appearance colorless needles (i-Pr₂ O)

mp 78.5°˜79.5° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 61.04; H, 6.95; N, 2.95

Example 42 Methyl 4-[4-[1-(phenylsulfonylamino)hexyl]phenyl]butyrate

Appearance colorless viscous oil

IR spectrum ν (liq) cm⁻¹ : 3288, 1738

NMR spectrum δ (CDCl₃) ppm: 0.81(3H,t,J=6.5 Hz),1.04-1.30(6H,m),1.60-1.70(1H,m),1.70-1.80(1H,m),1.88(2H,qn,J=7.5 Hz),2.28(2H,t,J=7.5 Hz),2.54(2H,t,J=7.5 Hz),3.68(3H,s ),4.27(1H,q,J=7.5 Hz),4.91-4.96(1H,m),6.90(2H,d,J=8 Hz),6.93(2H,d,J=8 Hz),7.29(2H,t,J=7.5 Hz),7.41(1H,t,J=7.5 Hz),7.63(2H,d,J=7.5 Hz)

Example 43 Methyl 4-[4-[1-(4-Bromophenylsulfonylamino)hexyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 82°˜83° C.

Analysis for C₂₃ H₃₀ BrNO₄ S

Calculated C, 55.64; H, 6.09; N, 2.82 Found C, 55.47; H, 6.06; N, 2.80

Example 44 Methyl 4-[4-[1-(4-Fluorophenylsulfonylamino)hexyl]phenyl]butyrate

Appearance colorless viscous oil

IR spectrum ν (liq) cm⁻¹ : 3288, 1738

NMR spectrum δ (CDCl₃) ppm: 0.82(3H,t,J=7 Hz),1.05-1.33(6H,m),1.60-1.70(1H,m),1.70-1.80(1H,m),1.88(2H,qn,J=7.5 Hz),2.29(2H,t,J=7.5 Hz),2.55(2H,t,J=7.5 Hz),3.68(3H,s),4.27(1H,q,J=7.5 Hz),4.85(1H,d,J=7.5 Hz),6.88(2H,d,J=8 Hz),6.94(2H,t,J=8.5 Hz),6.95(2H,d,J=8 Hz),7.59(2H,dd,J=8.5,5 Hz)

Example 45 Methyl 5-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]valerate

Appearance colorless needles (i-Pr₂ O)

mp 82°˜83.5° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.66; H, 7.20; N, 2.73

Example 46 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-methylhexyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 53°˜55° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.89; H, 7.02; N, 2.98

Example 47 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-methylheptyl]phenyl]butyrate

Appearance colorless prisms (n-Hexane)

mp 61.5°˜62.5° C.

Analysis for C₂₅ H₃₄ ClNO₄ S

Calculated C, 62.55; H, 7.14; N, 2.92 Found C, 62.50; H, 7.21; N, 2.92

Example 48 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O--AcOEt)

mp 104.5°˜106° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.71; H, 7.14; N, 3.03

Example 49 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O-n-Hexane)

mp 73.5°˜74.5° C.

Analysis for C₂₅ H₃₄ ClNO₄ S

Calculated C, 62.55; H, 7.14; N, 2.92 Found C, 62.52; H, 7.18; N, 2.71

Example 50 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O-n-Hexane)

mp 67.5°˜69° C.

Analysis for C₂₆ H₃₆ ClNO₄ S

Calculated C, 63.20; H, 7.34; N, 2.83 Found C, 63.09; H, 7.35; N, 2.70

Example 51 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-cyclopentylpropyl]phenyl]butyrate

Appearance colorless needles (MeOH)

mp 104°˜105° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.64; H, 6.85; N, 2.69

Example 52 Methyl 5-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]valerate

Appearance colorless crystals (AcOEt-i-Pr₂ O)

mp 102.5°˜104.5° C.

Analysis for C₂₆ H₃₄ ClNO₄ S

Calculated C, 63.46; H, 6.96; N, 2.85 Found C, 63.42; H, 7.01; N, 2.83

Example 53 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-phenylbutyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O)

mp 73.5°˜74.5° C.

Analysis for C₂₇ H₃₀ ClNO₄ S

Calculated C, 64.85; H, 6.05; N, 2.80 Found C, 64.93; H, 5.99; N, 2.78

Example 54 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-phenylpentyl]phenyl]butyrate

Appearance colorless prisms (EtOH)

mp 94°˜95.5° C.

Analysis for C₂₈ H₃₂ ClNO₄ S

Calculated C, 65.42; H, 6.27; N, 2.72 Found C, 65.24; H, 6.14; N, 2.75

Example 55 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-phenylhexyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 67°˜68° C.

Analysis for C₂₉ H₃₄ ClNO₄ S

Calculated C, 65.96; H, 6.49; N, 2.65 Found C, 65.83; H, 6.35; N, 2.69

Example 56 Methyl 4-[4-[3-(4-Butylphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

Appearance colorless viscous oil

IR spectrum ν (liq) cm⁻¹ : 3288, 1738

NMR spectrum δ (CDCl₃) ppm: 0.92(3H,t,J=7.5 Hz),1.35(2H,sex,J=7.5 Hz),1.54-1.61(2H,m),1.89(2H,qn,J=7.5 Hz),1.94-2.03(1H,m),2.05-2.14(1H,m),2.31(2H,t,J=7.5 Hz),2.44-2.55(2H,m),2.57(4H,t,J=8 Hz),3.68(3H,s),4.28(1H,q,J=7.5 Hz),5.07(1H,d,J=7.5 Hz),6.88(2H,d,J=8 Hz),6.95(2H,d,J=8 Hz),6.97(2H,d,J=8 Hz),7.06(2H,d,J=8 Hz),7.21(2H,d,J=8.5 Hz),7.48(2H,d,J=8.5 Hz)

Example 57 Methyl 4-[4-[3-(4-Butoxyphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 70.5°˜72.5° C.

Analysis for C₃₀ H₃₆ ClNO₅ S

Calculated C, 64.56; H, 6.50; N, 2.51 Found C, 64.61; H, 6.59; N, 2.47

Example 58 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(p-tolyl)propyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O--AcOEt)

mp 83°˜84.5° C.

Analysis for C₂₇ H₃₀ ClNO₄ S

Calculated C, 64.85; H, 6.05; N, 2.80 Found C, 64.87; H, 6.10; N, 2.78

Example 59 Methyl 4-[4-[3-(4-Chlorophenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyrate

Appearance colorless prisms (i-Pr₂ O)

mp 71°˜72.5° C.

Analysis for C₂₆ H₂₇ Cl₂ NO₄ S

Calculated C, 60.00; H, 5.23, N, 2.69 Found C, 60.29; H, 5.13; N, 2.79

Example 60 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(4-fluorophenyl)propyl]phenyl]butyrate

Appearance colorless oil

IR spectrum ν (liq) cm⁻¹ : 3284, 1738

NMR spectrum δ (CDCl₃) ppm: 1.89(2H,qn,J=7.5 Hz),1.93-2.02(1H,m),2.05-1.03(1H,m),2.31(2H,t,J=7.5 Hz),2.47-2.59(2H,m),2.56(2H,t,J=7.5 Hz),3.68(3H,s),4.25(1H,q,J,=7.5 Hz),5.00(1H,d,J=7.5 Hz),6.85(2H,d,J=8.5 Hz),6.95(4H,d,J=8.5 Hz),7.03(2H,dd,J=8.5,5.5 Hz),7.22(2H,d,J=8.5 Hz),7.48(2H,d,J=8.5 Hz)

Example 61 Methyl 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(3-fluorophenyl)propyl]phenyl]butyrate

Appearance colorless needles (i-Pr₂ O--MeOH)

mp 75.5°˜76° C.

Analysis for C₂₆ H₂₇ ClFNO₄ S

Calculated C, 61.96; H, 5.40; N, 2.78 Found C, 61.89; H, 5.41; N, 2.77

Example 62 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

To a suspension of 2.00 g of methyl 4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyrate in 17 ml of methanol, 7.7 ml of 2N aqueous sodium hydroxide was added and stirring was continued at room temperature for 2 hours. The solvent was removed under reduced pressure. The residue was added with water, acidified with dilute hydrochloric acid, and then extracted with methylene chloride. After the methylene chloride layer was washed with water and dried, the solvent was removed under reduced pressure to yield 1.87 g of colorless crystals. Recrystallization from a mixture of isopropyl ether and ethyl acetate gave colorless needles, mp 152°˜153° C.

Analysis for C₂₄ H₂₄ ClNO₄ S

Calculated C, 62.94; H, 5.28; N, 3.06 Found C, 62.76; H, 5.43; N, 3.03

The compounds of Examples 63 through 122 were obtained in the same manner as described in Example 62.

Example 63 4-[4-[1-(4-Chlorophenylsulfonylamino)ethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 98°˜98.5° C.

Analysis for C₁₈ H₂₀ ClNO₄ S

Calculated C, 56.61; H, 5.28; N, 3.67 Found C, 56.59; H, 5.24; N, 3.61

Example 64 4-[4-[1-(4-Chlorophenylsulfonylamino)propyl]phenyl]butyric Acid

Appearance colorless columns (AcOEt-i-Pr₂ O)

mp 120°˜121° C.

Analysis for C₁₉ H₂₂ ClNO₄ S

Calculated C, 57.64; H, 5.60; N, 3.54 Found C, 57.63; H, 5.63; N, 3.49

Example 65 4-[4-[1-(4-Chlorophenylsulfonylamino)butyl]phenyl]butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 111.5°˜112.5° C.

Analysis for C₂₀ H₂₄ ClNO₄ S

Calculated C, 58.60; H, 5.90; N, 3.42 Found C, 58.57; H, 6.09; N, 3.46

Example 66 4-[4-[1-(4-Chlorophenylsulfonylamino)pentyl]phenyl]butyric Acid

Appearance colorless prisms (90% aq. MeOH)

mp 119°˜120.5° C.

Analysis for C₂₁ H₂₆ ClNO₄ S

Calculated C, 59.49; H, 6.18; N, 3.30 Found C, 59.40; H, 6.31; N, 3.32

Example 67 4-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]butyric Acid

Appearance colorless prisms (80% aq. MeOH)

mp 117°˜118° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.26; H, 6.70; N, 3.23

Example 68 4-[4-[1-(4-Chlorophenylsulfonylamino)decyl]phenyl]butyric Acid

Appearance colorless prisms (i-Pr₂ O)

mp 99.5°˜100.5° C.

Analysis for C₂₆ H₃₆ ClNO₄ S

Calculated C, 63.20; H, 7.34; N, 2.83 Found C, 63.11; H, 7.63; N, 2.80

Example 69 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 121.5°˜122.5° C.

Analysis for C₂₀ H₂₄ ClNO₄ S

Calculated C, 58.60; H, 5.90; N, 3.42 Found C, 58.56; H, 5.84; N, 3.56

Example 70 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-methylbutyl]phenyl]butyric Acid

Appearance colorless needles (80% aq.MeOH)

mp 139.5°˜141.5° C.

Analysis for C₂₁ H₂₆ ClNO₄ S

Calculated C, 59.49; H, 6.18; N, 3.30 Found C, 59.45; H, 6.38; N, 3.33

Example 71 4-[4-[1-(4-Chlorophenylsulfonylamino)-4-methylpentyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 139°˜140.5° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.18; H, 6.67; N, 3.24

Example 72 4-[4-[1-(4-Chlorophenylsulfonylamino)-3,3-dimethylbutyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 150°˜151° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.30; H, 6.66; N, 3.26

Example 73 4-[4-[(4-Chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 139.5°˜140° C.

Analysis for C₂₂ H₂₆ ClNO₄ S

Calculated C, 60.61; H, 6.01; N, 3.21 Found C, 60.52; H, 5.98; N, 3.36

Example 74 4-[4-[(4-Chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric Acid

Appearance colorless needles (i-PrOH-i-Pr₂ O)

mp 151°˜152.5° C.

Analysis for C₂₃ H₂₈ ClNO₄ S

Calculated C, 61.39; H, 6.27; N, 3.11 Found C, 61.13; H, 6.20; N, 3.21

Example 75 4-[4-[(4-Chlorophenylsulfonylamino)cycloheptylmethyl]phenyl]butyric Acid

Appearance colorless prisms (80% aq. MeOH)

mp 132.5°˜133.5° C.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 61.99; H, 6.72; N, 2.99

Example 76 trans-4-[4-[(4-Chlorophenylsulfonylamino)(4-methylcyclohexyl)methyl]phenyl]butyric Acid

Appearance colorless plates (90% aq. MeOH)

mp 167.5°˜168.5° C.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 61.89; H, 6.78; N, 3.23

Example 77 trans-4-[4-[(4-Chlorophenylsulfonylamino)(4-pentylcyclohexyl)methyl]phenyl]butyric Acid

Appearance colorless needles (95% aq. MeOH)

mp 157.5°˜159.5° C.

Analysis for C₂₈ H₃₈ ClNO₄ S

Calculated C, 64.66; H, 7.36; N, 2.69 Found C, 64.79; H, 7.63; N, 2.65

Example 78 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclopentylethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 163°˜164° C.

Analysis for C₂₃ H₂₈ ClNO₄ S

Calculated C, 61.39; H, 6.27; N, 3.11 Found C, 61.26; H, 6.49; N, 3.12

Example 79 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 146°˜148° C.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 62.00; H, 6.77; N, 3.08

Example 80 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-cyclohexylpropyl]phenyl]butyric Acid

Appearance colorless prisms (85% aq. MeOH)

mp 141.5°˜143° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.67; H, 6.84; N, 2.93

Example 81 4-[4-[1-(4-Chlorophenylsulfonylamino)-4-cyclohexylbutyl]phenyl]butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 123.5°˜125° C.

Analysis for C₂₆ H₃₄ ClNO₄ S

Calculated C, 63.46; H, 6.96; N, 2.85 Found C, 63.33; H, 7.10; N, 2.93

Example 82 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-cyclohexylpentyl]phenyl]butyric Acid

Appearance colorless crystals (90% aq. MeOH)

mp 119°˜121° C.

Analysis for C₂₇ H₃₆ ClNO₄ S

Calculated C, 64.08; H, 7.17; N, 2.77 Found C, 64.02; H, 7.25; N, 2.71

Example 83 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-cyclohexylhexyl]phenyl]butyric Acid

Appearance colorless crystals (90% aq.MeOH)

mp 130°˜131° C.

Analysis for C₂₈ H₃₈ ClNO₄ S

Calculated C, 64.66; H, 7.36; N, 2.69 Found C, 64.60; H, 7.49; N, 2.64

Example 84 4-[4-[2-(1-Adamantyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric Acid

Appearance colorless needles (85% aq.MeOH)

mp 154.5°˜155° C.

Analysis for C₂₈ H₃₄ ClNO₄ S

Calculated C, 65.16; H, 6.64; N, 2.71 Found C, 64.98; H, 6.81; N, 2.64

Example 85 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(2-norbornyl)ethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 147°˜148.5° c.

Analysis for C₂₅ H₃₁ ClNO₄ S

Calculated C, 62.94; H, 6.55; N, 2.94 Found C, 63.02; H, 6.51; N, 2.90

Example 86 3-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]propionic Acid

Appearance colorless plates (EtOH)

mp 141.5°˜142.5° C.

Analysis for C₂₃ H₂₂ ClNO₄ S

Calculated C, 62.23; H, 4.99; N, 3.16 Found C, 62.25; H, 5.14; N, 3.10

Example 87 4-[4-[2-phenyl-1-(phenylsulfonylamino)ethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 121.5°˜123° C.

Analysis for C₂₄ H₂₅ NO₄ S

Calculated C, 68.06; H, 5.95; N, 3.31 Found C, 68.09; H, 6.09; N, 3.25

Example 88 4-[4-[1-(4-Fluorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 134.5°˜136° C.

Analysis for C₂₄ H₂₄ FNO₄ S

Calculated C, 65.29; H, 5.48; N, 3.17 Found C, 65.23; H, 5.52; N, 3.11

Example 89 4-[4-[1-(4-Bromophenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 154.5°˜155.5° C.

Analysis for C₂₄ H₂₄ BrNO₄ S

Calculated C, 57.37; H, 4.81; N, 2.79 Found C, 57.35; H, 4.81; N, 2.77

Example 90 4-[4-[1-(p-Tolylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

Appearance colorless prisms (AcOEt-i-Pr₂ O)

mp 161.5°˜162.5° C.

Analysis for C₂₅ H₂₇ NO₄ S

Calculated C, 68.62; H, 6.22; N, 3.20 Found C, 68.44; H, 6.36; N, 3.12

Example 91 4-[4-[1-(4-Methoxyphenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

Appearance colorless needles (AcOEt-i-Pr₂ O)

mp 141.5°˜142.5° C.

Analysis for C₂₅ H₂₇ NO₅ S

Calculated C, 66.20; H, 6.00; N, 3.09 Found C, 66.28; H, 6.11; N, 3.04

Example 92 5-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]valeric Acid

Appearance colorless prisms (MeOH)

mp 186°˜187.5° C.

Analysis for C₂₅ H₂₆ ClNO₄ S

Calculated C, 63.62; H, 5.35; N, 2.97 Found C, 63.44; H, 5.76; N, 2.97

Example 93 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(2-fluorophenyl)ethyl]phenyl]butyric Acid

Appearance colorless needles (90% aq.MeOH)

mp 149.5°˜150.5° C.

Analysis for C₂₄ H₂₃ ClFNO₄ S

Calculated C, 60.56; H, 4.87; N, 2.94 Found C, 60.60; H, 4.79; N, 2.92

Example 94 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyric Acid

Appearance colorless prisms (90% aq. MeOH)

mp 157°˜159° C.

Analysis for C₂₄ H₂₃ ClFNO₄ S

Calculated C, 60.56; H, 4.87; N, 2.94 Found C, 60.64; H, 4.85; N, 2.88

Example 95 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(4-fluorophenyl)ethyl]phenyl]butyric Acid

Appearance colorless prisms (90% aq. MeOH)

mp 166°˜167.5° C.

Analysis for C₂₄ H₂₃ ClFNO₄ S

Calculated C, 60.56; H, 4.87; N, 2.94 Found C, 60.59; H, 4.88; N, 2.92

Example 96 4-[4-[2-(4-Chlorophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric Acid

Appearance colorless prisms (MeOH)

mp 169.5°˜171° C.

Analysis for C₂₄ H₂₃ Cl₂ NO₄ S

Calculated C, 58.54; H, 4.71; N, 2.84 Found C, 58.60; H, 4.65; N, 2.85

Example 97 4-[4-[1-(4-Chlorophenylsulfonylamino)-2-(p-tolyl)ethyl]phenyl]butyric Acid

Appearance colorless columns (AcOEt-i-Pr₂ O)

mp 148°-148.5° C.

Analysis for C₂₅ H₂₈ ClNO₄ S

Calculated C, 63.62; H, 5.55; N, 2.97 Found C, 63.53; H, 5.63; N, 2.96

Example 98 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-phenylpropyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 114.5°˜116° C.

Analysis for C₂₅ H₂₆ ClNO₄ S

Calculated C, 63.62; H, 5.55; N, 2.97 Found C, 63.42; H, 5.53; N, 3.01

Example 99 4-[4-[1-(4-Chlorophenylsulfonylamino)heptyl]phenyl]butyric Acid

Appearance colorless prisms (80% aq.MeOH)

mp 106°˜108.5° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 61.00; H, 6.84; N, 3.20

Example 100 4-[4-[1-(4-Chlorophenylsulfonylamino)octyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 88°-89° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.75; H, 7.08; N, 3.10

Example 101 4-[4-[1-(4-Chlorophenylsulfonylamino)nonyl]phenyl]butyric Acid

Appearance colorless plates (80% aq. MeOH)

mp 101.5°˜103° C.

Analysis for C₂₅ H₃₄ ClNO₄ S

Calculated C, 62.55; H, 7.14; N, 2.92 Found C, 62.31; H, 7.34; N, 3.07

Example 102 5-[4-[1-(4-Chlorophenylsulfonylamino)pentyl]phenyl]valeric Acid

Appearance colorless prisms (80% aq. MeOH)

mp 106°˜107.5° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.28; H, 6.64; N, 3.07

Example 103 4-[4-[1-(Phenylsulfonylamino)hexyl]phenyl]butyric Acid

Appearance colorless prisms (75% aq.MeOH)

mp 125°˜126.5° C.

Analysis for C₂₂ H₂₉ NO₄ S

Calculated C, 65.48; H, 7.24; N, 3.47 Found C, 65.39; H, 7.42; N, 3.41

Example 104 4-[4-[1-(4-Bromophenylsulfonylamino)hexyl]phenyl]butyric Acid

Appearance colorless needles (75% aq. MeOH)

mp 123°˜124.5° C.

Analysis for C₂₂ H₂₈ BrNO₄ S

Calculated C, 54.77; H, 5.85; N, 2.90 Found C, 54.53; H, 5.98; N, 2.89

Example 105 4-[4-[1-(4-Fluorophenylsulfonylamino)hexyl]phenyl]butyric Acid

Appearance colorless prisms (75% aq. MeOH)

mp 114°˜116° C.

Analysis for C₂₂ H₂₈ FNO₄ S

Calculated C, 62.69; H, 6.70; N, 3.32 Found C, 62.48; H, 6.81; N, 3.27

Example 106 5-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]valeric Acid

Appearance colorless prisms (80% aq. MeOH)

mp 85°˜86.5° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 61.08; H, 6.93; N, 3.06

Example 107 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-methylhexyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 124°˜126° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10 Found C, 61.04; H, 6.86; N, 3.13

Example 108 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-methylheptyl]phenyl]-butyric Acid

Appearance colorless prisms (80% aq. MeOH)

mp 113°˜114° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.64; H, 7.12; N, 2.99

Example 109 4-[4-[1-(4-Chlorophenylsulfonylamino)-4,4-dimethylpentyl]phenyl]butyric Acid

Appearance colorless prisms (MeOH)

mp 141.5°˜144.5° C.

Analysis for C₂₃ H₃₀ ClNO₄ S

Calculated C, 61.12; H, 6.69; N, 3.10

Found C, 61.11; H, 6.99; N, 2.83

Example 110 4-[4-[1-(4-Chlorophenylsulfonylamino)-5,5-dimethylhexyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 114.5°˜115.5° C.

Analysis for C₂₄ H₃₂ ClNO₄ S

Calculated C, 61.85; H, 6.92; N, 3.01 Found C, 61.80; H, 6.80; N, 2.87

Example 111 4-[4-[1-(4-Chlorophenylsulfonylamino)-6,6-dimethylheptyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 132.5°˜134.5° C.

Analysis for C₂₅ H₃₄ ClNO₄ S

Calculated C, 62.55; H, 7.14; N, 2.92 Found C, 62.45; H, 7.04; N, 2.74

Example 112 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-cyclopentylpropyl]phenyl]butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 135°˜136° c.

Analysis for C₂₄ H₃₀ ClNO₄ S

Calculated C, 62.12; H, 6.52; N, 3.02 Found C, 62.01; H, 6.58; N, 2.99

Example 113 5-[4-[1-(4-Chlorophenylsulfonylamino)-2-cyclohexylethyl]phenyl]valeric Acid

Appearance colorless prisms (MeOH)

mp 156.5°˜158.5° C.

Analysis for C₂₅ H₃₂ ClNO₄ S

Calculated C, 62.81; H, 6.75; N, 2.93 Found C, 62.79; H, 7.03; N, 2.80

Example 114 4-[4-[1-(4-Chlorophenylsulfonylamino)-4-phenylbutyl]phenyl]butyric Acid

Appearance colorless plates (80% aq.MeOH)

mp 130.5°˜132.5° C.

Analysis for C₂₆ H₂₈ ClNO₄ S

Calculated C, 64.25; H, 5.81; N, 2.88 Found C, 64.11; H, 5.63; N, 2.89

Example 115 4-[4-[1-(4-Chlorophenylsulfonylamino)-5-phenylpentyl]phenyl]-butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 102.5°˜103.5° C.

Analysis for C₂₇ H₃₀ ClNO₄ S

Calculated C, 64.85; H, 6.05; N, 2.80 Found C, 64.66; H, 5.96; N, 2.85

Example 116 4-[4-[1-(4-Chlorophenylsulfonylamino)-6-phenylhexyl]phenyl]butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 120.5°˜122.5° C.

Example 117 4-[4-[3-(4-Butylphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric Acid

Appearance colorless needles (80% aq. MeOH)

mp 113°˜114° C.

Analysis for C₂₉ H₃₄ ClNO₄ S

Calculated C, 65.96; H, 6.49; N, 2.65 Found C, 65.93; H, 6.58; N, 2.64

Example 118 4-[4-[3-(4-Butoxyphenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric Acid

Appearance colorless plates (90% aq. MeOH)

mp 115°˜117.5° C.

Analysis for C₂₉ H₃₄ ClNO₅ S

Calculated C, 64.02; H, 6.30; N, 2.57 Found C, 63.99; H, 6.56; N, 2.53

Example 119 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(p-tolyl)propyl]phenyl]butyric Acid

Appearance colorless needles (90% aq. MeOH)

mp 139°˜141° C.

Analysis for C₂₆ H₂₈ ClNO₄ S

Calculated C, 64.25; H, 5.81; N, 2.88 Found C, 64.19; H, 5.54; N, 3.02

Example 120 4-[4-[3-(4-Chlorophenyl)-1-(4-chlorophenylsulfonylamino)propyl]phenyl]butyric Acid

Appearance colorless needles (80% aq.MeOH)

mp 123.5°˜124.5° C.

Analysis for C₂₅ H₂₅ Cl₂ NO₄ S

Calculated C, 59.29; H, 4.98; N, 2.77 Found C, 59.42; H, 4.78; N, 2.80

Example 121 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(4-fluorophenyl)propyl]phenyl]butyric Acid

Appearance colorless prisms (80% aq.MeOH)

mp 126°˜127.5° C.

Analysis for C₂₅ H₂₅ ClFNO₄ S

Calculated C, 61.28; H, 5.14; N, 2.86 Found C, 61.35; H, 5.19; N, 2.80

Example 122 4-[4-[1-(4-Chlorophenylsulfonylamino)-3-(3-fulorophenyl)propyl]phenyl]butyric Acid

Appearance colorless plates (80% aq.MeOH)

mp 139°·140.5° C.

Analysis for C₂₅ H₂₅ ClFNO₄ S

Calculated C, 61.28; H, 5.14; N, 2.86 Found C, 61.16; H, 5.03; N, 2.76

Example 123 (+)-4-[4-[1-(4-Chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric Acid

10.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric acid and 7.91 g of quinidine were dissolved in 60 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 8.65 g of colorless crystals. The results were recrystallized twice from ethanol to give 7.11 g of quinidine salt of the title compound as colorless prisms, mp 185°˜186° C.

Analysis for C₂₀ H₂₄ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 65.42; H, 6.59; N, 5.72 Found C, 65.24; H, 6.61; N, 6.00 Specific rotation [α]²⁰ _(D) +126.8° (c=1,MeOH)

The quinidine salt obtained above was added to dilute hydrochloric acid and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from a mixture of isopropyl ether and ethyl acetate to give 3.24 g of the title compound as colorless needles, mp 117°˜119° C.

Analysis for C₂₀ H₂₄ ClNO₄ S

Calculated C, 58.60; H, 5.90; N, 3.42 Found C, 58.49; H, 5.91; N, 3.60 Specific rotation [α]²⁰ _(D) +9.1° (c=1,MeOH)

Example 124 (-)-4-[4-[1-(4-Chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric Acid

4.65 g of free acid, recovered in an ordinary manner from the residue obtained from the filtrate that was recovered after the salt formation between 10.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-methylpropyl]phenyl]butyric acid and 7.91 g of quinidine, and 4.08 g of quinine were dissolved in 30 ml of ethyl acetate. After cooling, crystals precipitated were collected by filtration to give 7.60 g of colorless crystals. The results were recrystallized successively once from ethanol and once from methanol to give 6.41 g of quinine salt of the title compound as colorless needles, mp 185°˜186° C.

Analysis for C₂₀ H₂₄ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 65.42; H, 6.59; N, 5.72 Found C, 65.19; H, 6.54; N, 5.89 Specific rotation [α]²⁰ _(D) -101.6° (c=1,MeOH)

The quinine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from a mixture of isopropyl ether and ethyl acetate to give 2.89 g of the title compound as colorless needles, mp 116.5°˜119° C.

Analysis for C₂₀ H₂₄ ClNO₄ S

Calculated C, 58.60; H, 5.90; N, 3.42 Found C, 58.49; H, 5.84; N, 3.63 Specific rotation [α]²⁰ _(D) -9.1° (c=1,MeOH)

Example 125 (-)-4-[4-[(4-Chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric Acid

7.00 g of (±)-4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid and 5.21 g of quinidine were dissolved in 45 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 6.78 g of colorless crystals. The results were recrystallized twice from isopropanol and once from ethanol to give 4.83 g of quinidine salt of the title compound as colorless needles, mp 178.5°˜180.5° C.

Analysis for C₂₂ H₂₆ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.34; H, 6.63; N, 5.53 Found C, 66.21; H, 6.64; N, 5.48 Specific rotation [α]²⁰ _(D) +115.0° (c=1,MeOH)

The quinidine salt obtained above was added to dilute hydrochloric acid and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 90% aqueous methanol to give 2.15 g of the title compound as colorless needles, mp 160°˜162° C.

Analysis for C₂₂ H₂₆ ClNO₄ S

Calculated C, 60.61; H, 6.01; N, 3.21 Found C, 60.80; H, 6.01; N, 3.20 Specific rotation [α]²⁰ _(D) -6.2° (c=1,MeOH)

Example 126 (+)-4-[4-[(4-Chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric Acid

3.54 g of free acid, recovered in an ordinary manner from the residue obtained from the filtrate that was recovered after the salt formation between 7.00 g of (±)-4-[4-[(4-chlorophenylsulfonylamino)cyclopentylmethyl]phenyl]butyric acid and 5.21 g of quinidine, and 2.92 g of quinine were dissolved in 15 ml of ethyl acetate. After cooling, crystals precipitated were collected by filtration to give 4.57 g of colorless crystals. The results were recrystallized successively once from isopropanol and once from ethanol to give 4.90 g of quinine salt of the title compound as colorless prisms, mp 177°˜179° C.

Analysis for C₂₂ H₂₆ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.34; H, 6.63; N, 5.53 Found C, 66.17; H, 6.61; N, 5.47 Specific rotation [α]²⁰ _(D) -84.4° (c=1,MeOH)

The quinine salt obtained above was added to dilute hydrochloric acid and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 90% aqueous methanol to give 2.13 g of the title compound as colorless needles, mp 160°˜162° C.

Analysis for C₂₂ H₂₆ ClNO₄ S

Calculated C, 60.61; H, 6.01; N, 3.21 Found C, 60.63; H, 5.99; N, 3.14 Specific rotation [α]²⁰ _(D) +5.8° (c=1,MeOH)

Example 127 (+)-4-[4-[(4-Chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric Acid

10.00 g of (±)-4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric acid and 7.21 g of quinidine were dissolved in 40 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 8.38 g of colorless crystals. Recrystallization from isopropanol gave 6.61 g quinidine salt of the title compound as colorless prisms, mp 173°˜174° C.

Analysis for C₂₃ H₂₈ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.69; H, 6.77; N, 5.43 Found C, 66.55; H, 6.85; N, 5.30 Specific rotation [α]²⁰ _(D) +115.3° (c=1,MeOH)

The quinidine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 80% aqueous methanol to give 3.24 g of the title compound as colorless needles, mp 165°˜166° C.

Analysis for C₂₃ H₂₈ ClNO₄ S

Calculated C, 61.39; H, 6.27; N, 3.11 Found C, 61.46; H, 6.20; N, 3.06 Specific rotation [α]²⁰ _(D) +3.1° (c=1,MeOH)

Example 128 (-)-4-[4-[(4-Chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric Acid

4.70 g of free acid, recovered in an ordinary manner from the residue obtained from the filtrate that was recovered after the salt formation between 10.00 g of (±)-4-[4-[(4-chlorophenylsulfonylamino)cyclohexylmethyl]phenyl]butyric acid and 7.21 g of quinidine, and 3.78 g of quinine were dissolved in 20 ml of ethyl acetate. After cooling, crystals precipitated were collected by filtration to give 6.80 g of colorless crystals. The results were recrystallized from isopropanol to give 6.26 g of quinine salt of the title compound as colorless prisms, mp 176°˜177° C.

Analysis for C₂₃ H₂₈ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.69; H, 6.77; N, 5.43 Found C, 66.41; H, 6.91; N, 5.22 Specific rotation [α]²⁰ _(D) -86.2° (c=1,MeOH)

The quinine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 80% aqueous methanol to give 3.03 g of the title compound as colorless needles, mp 165°˜166° C.

Analysis for C₂₃ H₂₈ ClNO₄ S

Calculated C, 61.39; H, 6.27; N, 3.11 Found C, 61.47; H, 6.20; N, 3.12 Specific rotation [α]²⁰ _(D) -3.3° (c=1,MeOH)

Example 129 (-)-4-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

10.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid and 7.08 g of quinidine were dissolved in 70 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 8.02 g of colorless crystals. The results were recrystallized from methanol to give 6.37 g of quinidine salt of the title compound as colorless prisms, mp 181.5°˜183.5° C.

Analysis for C₂₄ H₂₄ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 67.55; H, 6.18; N, 5.37 Found C, 67.48; H, 6.17; N, 5.50 Specific rotation [α]²⁰ _(D) +93.6° (c=1,MeOH)

The quinidine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 90% aqueous ethanol to give 3.14 g of the title compound as colorless needles, mp 173.5°˜174° C.

Analysis for C₂₄ H₂₄ ClNO₄ S

Calculated C, 62.94; H, 5.28; N, 3.06 Found C, 62.94; H, 5.19; N, 3.17 Specific rotation [α]²⁰ _(D) -40.3° (c=1,MeOH)

Example 130 (+)-4-[4-[1-(4-Chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric Acid

5.00 g of free acid, recovered in an ordinary manner from the residue obtained from the filtrate that was recovered after the salt formation between 10.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid and 7.08 g of quinidine, and 3.92 g of quinine were dissolved in 40 ml of ethyl acetate. After cooling, crystals precipitated were collected by filtration to give 7.50 g of colorless crystals. The results were recrystallized from ethanol to give 6.50 g of quinine salt of the title compound as colorless prisms, mp 174°˜176° C.

Analysis for C₂₄ H₂₄ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 67.55; H, 6.18; N, 5.37 Found C, 67.42; H, 6.16; N, 5.43 Specific rotation [α]²⁰ _(D) -63.7° (c=1,MeOH)

The quinine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and the solvent was removed. The resulting residue was recrystallized from 90% aqueous ethanol to give 3.06 g of the title compound as colorless needles, mp 173°˜174° C.

Analysis for C₂₄ H₂₄ ClNO₄ S

Calculated C, 62.94; H, 5.28; N, 3.06 Found C, 62.89; H, 5.30; N, 3.26 Specific rotation [α]²⁰ _(D) +40.2° (c=1,MeOH)

Example 131 (-)-4-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]butyric Acid

8.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid and 6.58 g of quinine were dissolved in 45 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 6.53 g of colorless crystals. The results were recrystallized twice from 90% aqueous ethanol to give 4.71 g of quinine salt of the title compound as colorless prisms, mp 166.5°˜170° C.

Analysis for C₂₂ H₂₈ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.17; H, 6.87; N, 5.51 Found C, 66.08; H, 6.97; N, 5.39 Specific rotation [α]²⁰ _(D) -95.0° (c=1,MeOH)

The quinine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and the solvent was removed. The resulting residue was recrystallized from 80% aqueous methanol to give 2.35 g of the title compound as colorless needles, mp 134.5°˜137° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.40; H, 6.65; N, 3.34 Specific rotation [α]²⁰ _(D) -10.7° (c=1,MeOH)

Example 132 (+)-4-[4-[1-(4-Chlorophenylsulfonylamino)hexyl]phenyl]butyric Acid

4.60 g of free acid, recovered in an ordinary manner from the residue obtained from the filtrate that was recovered after the salt formation between 8.00 g of (±)-4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid and 6.58 g of quinine, and 3.41 g of quinidine were dissolved in 20 ml of ethyl acetate by heating. After cooling, crystals precipitated were collected by filtration to give 6.00 g of colorless crystals. The results were recrystallized twice from 80% aqueous ethanol to give 4.61 g of quinidine salt of the title compound as colorless prisms, mp 157°˜160° C.

Analysis for C₂₂ H₂₈ ClNO₄ S•C₂₀ H₂₄ N₂ O₂

Calculated C, 66.17; H, 6.87; N, 5.51 Found C, 66.09; H, 6.74; N, 5.41 Specific rotation [α]²⁰ _(D) +124.6° (c=1,MeOH)

The quinidine salt obtained above was added to dilute hydrochloric acid, and extraction was carried out using ethyl acetate. The ethyl acetate layer was washed with water and dried, and then the solvent was removed. The resulting residue was recrystallized from 80% aqueous methanol to give 2.27 g of the title compound as colorless needles; mp 133.5°˜136° C.

Analysis for C₂₂ H₂₈ ClNO₄ S

Calculated C, 60.33; H, 6.44; N, 3.20 Found C, 60.41; H, 6.66; N, 3.34 Specific rotation [α]²⁰ _(D) +11.2° (c=1,MeOH)

Example 133

A tablet is prepared according to the following formulation:

    ______________________________________     Compound of Example 67  50     mg     Lactose              q.s.     Corn starch             34     mg     Magnesium stearate      2      mg     Hydroxypropylmethylcellulose                             8      mg     Polyethyleneglycol 6000 0.5    mg     Titanium oxide          0.5    mg                             160    mg     ______________________________________

Example 134

A capsule is prepared according to the following formulation:

    ______________________________________     Compound of Example 67   50     mg     Lactose              q.s.     Calcium carboxymethylcellulose                              15     mg     Hydroxypropylcellulose   2      mg     Magnesium stearate       2      mg                              140    mg     ______________________________________

The above ingredients are mixed in an ordinary manner and filled into a hard capsule.

Example 135

Powder is prepared according to the following formulation:

    ______________________________________     Compound of Example 67  50     mg     Lactose             q.s.     D-Mannitol              500    mg     Hydroxypropylcellulose  5      mg     Talc                    2      mg                             1000   mg     ______________________________________

Example 136

Injection is prepared according to the following formulation:

    ______________________________________     Compound of Example 67  10     mg     Glucose                 100    mg     Sodium hydroxide    q.s.     Distilled water for injection                         q.s.                           2    ml     ______________________________________

INDUSTRIAL APPLICABILITY

The novel benzenesulfonamide derivatives of the present invention represented by the above Formula (I) and pharmacologically acceptable salts thereof are highly useful as platelet aggregation inhibitors, antithrombotic agents, antiasthmatic agents, antiallergic agents and the like. 

What is claimed is:
 1. A benzenesulfonamide derivative represented by the following general formula: ##STR8## wherein R¹ represents a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom; R² represents a C₂ -C₁₀ straight- or branched-chain alkyl group, a C₃ -C₈ cycloalkyl group which may be substituted with one or more C₁ -C₆ alkyl groups on its ring, a C₁ -C₆ alkyl group substituted with one or more C₃ -C₈ cycloalkyl groups, 1-adamantylmethyl group, 2-norbornylmethyl group, or a C₁ -C₆ alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents; R³ represents a hydrogen atom or a lower alkyl group; and n is an integer of from 2 to 4, and a pharmacologically acceptable salt thereof.
 2. The compound and pharmacologically acceptable salt thereof according to claim 1, wherein R¹ represents a halogen atom; R² represents a C₄ -C₈ straight- or branched-chain alkyl group or a C₁ -C₂ alkyl group substituted with one or more phenyl groups whose benzene ring may have one or more substituents; R³ represents a hydrogen atom or a lower alkyl group; and n is
 3. 3. The compound and pharmacologically acceptable salt thereof according to claim 2, wherein R¹ represents a halogen atom; R² represents a C₄ -C₈ straight- or branched-chain alkyl group, or benzyl group or phenethyl group which may be substituted with one or more halogen atoms or lower alkyl groups; R³ represents a hydrogen atom or a lower alkyl group; and n is
 3. 4. The compound and pharmacologically acceptable salt thereof according to claim 3 which is selected from the group consisting of:4-[4-[1-(4-chlorophenylsulfonylamino)pentyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenylsulfonylamino)hexyl]phenyl]butyric acid; 4-[4-[1-(4-fluorophenylsulfonylamino)hexyl]phenyl]butyric acid; 4-[4-[1-(4-bromophenylsulfonylamino)hexyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenylsulfonylamino)-6-methylheptyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenylsulfonylamino)-5-methylhexyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid; 4-[4-[1-(4-bromophenylsulfonylamino)-2-phenylethyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenylsulfonylamino)-2-(3-fluorophenyl)ethyl]phenyl]butyric acid; 4-[4-[2-(4-chlorophenyl)-1-(4-chlorophenylsulfonylamino)ethyl]phenyl]butyric acid; 4-[4-[1-(4-chlorophenyl)-2-(p-tolyl)ethyl]-phenyl]butyric acid; and mixtures thereof.
 5. A pharmaceutical composition for the treatment of an ailment due to elevated levels of Thromboxane A₂ or Leucotriene comprising a pharmaceutically effective amount of a benzenesulfonamide derivative of claim 1 in a pharmaceutically acceptable carrier.
 6. A unit dosage form for the treatment of an ailment due to elevated levels of thromboxane A₂ or leucotriene comprising a pharmaceutically effective amount of a benzenesulfonamide derivative of claim 1 in a pharmaceutically acceptable carrier.
 7. A unit dosage form according to claim 6, wherein the unit dosage is for oral or parenteral administration.
 8. A unit dosage form according to claim 6, for oral administration in the form of a tablet, capsule or powder.
 9. A method of treating thrombosis or excessive platelet aggregation by administering to a subject a pharmaceutically effective amount of a benzenesulfonamide derivative of claim 1 in a pharmaceutically effective carrier.
 10. A method of treating asthma by administering to a subject a pharmaceutically effective amount of a benzenesulfonamide derivative of claim 1 in a pharmaceutically effective carrier.
 11. A method of treating an allergy by administering to a subject a pharmaceutically effective amount of a benzenesulfonamide derivative of claim 1 in a pharmaceutically effective carrier. 